Timothy Billiar

Summary

Affiliation: University of Pittsburgh
Country: USA

Publications

  1. pmc HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 204:2913-23. 2007
  2. pmc Molecular analysis of transplant rejection: marching onward
    Fadi G Lakkis
    the Department of Surgery University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 F G Lakkis is at the Thomas E Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
    J Exp Med 210:2147-9. 2013
  3. pmc Toll-like receptors and myocardial ischemia/reperfusion, inflammation, and injury
    David J Kaczorowski
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
    Curr Cardiol Rev 5:196-202. 2009
  4. pmc Hydrogen inhalation ameliorates ventilator-induced lung injury
    Chien Sheng Huang
    Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Crit Care 14:R234. 2010
  5. pmc Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells
    Roop Gill
    Department of Surgery, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
    Shock 35:164-70. 2011
  6. ncbi request reprint Innate immune mechanisms in ischemia/reperfusion
    David J Kaczorowski
    Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Presbyterian Hospital F1200, Pittsburgh, PA 15213, USA
    Front Biosci (Elite Ed) 1:91-8. 2009
  7. ncbi request reprint Carbon monoxide prevents multiple organ injury in a model of hemorrhagic shock and resuscitation
    Brian S Zuckerbraun
    Department of Surgery, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Shock 23:527-32. 2005
  8. pmc High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity
    John Evankovich
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 285:39888-97. 2010
  9. pmc Role of toll-like receptors in changes in gene expression and NF-kappa B activation in mouse hepatocytes stimulated with lipopolysaccharide
    Shubing Liu
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Infect Immun 70:3433-42. 2002
  10. pmc Complement factor 3 deficiency attenuates hemorrhagic shock-related hepatic injury and systemic inflammatory response syndrome
    Changchun Cai
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA
    Am J Physiol Regul Integr Comp Physiol 299:R1175-82. 2010

Research Grants

Detail Information

Publications92

  1. pmc HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 204:2913-23. 2007
    ..Collectively, these results demonstrate that hypoxia-induced HMGB1 release by hepatocytes is an active, regulated process that occurs through a mechanism promoted by TLR4-dependent ROS production and downstream CaMK-mediated signaling...
  2. pmc Molecular analysis of transplant rejection: marching onward
    Fadi G Lakkis
    the Department of Surgery University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 F G Lakkis is at the Thomas E Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
    J Exp Med 210:2147-9. 2013
    ..These advances hold significant promise for the treatment of organ rejection and for improving clinical outcomes after transplantation, but hurdles remain. ..
  3. pmc Toll-like receptors and myocardial ischemia/reperfusion, inflammation, and injury
    David J Kaczorowski
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
    Curr Cardiol Rev 5:196-202. 2009
    ..This emerging body of literature, which is reviewed here, has provided new insight into the early molecular events that mediate myocardial injury and dysfunction in the setting of I/R injury...
  4. pmc Hydrogen inhalation ameliorates ventilator-induced lung injury
    Chien Sheng Huang
    Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Crit Care 14:R234. 2010
    ..Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI...
  5. pmc Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells
    Roop Gill
    Department of Surgery, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
    Shock 35:164-70. 2011
    ..These data suggest that release of DNA may be a driver of the inflammatory response to severe injury as well as a marker of the extent of tissue damage. One of the sensors of DNA in the setting of HS/T seems to be TLR9...
  6. ncbi request reprint Innate immune mechanisms in ischemia/reperfusion
    David J Kaczorowski
    Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Presbyterian Hospital F1200, Pittsburgh, PA 15213, USA
    Front Biosci (Elite Ed) 1:91-8. 2009
    ..This evolving body of literature, which has provided insight into the early molecular events that activate the innate system after I/R, is reviewed here...
  7. ncbi request reprint Carbon monoxide prevents multiple organ injury in a model of hemorrhagic shock and resuscitation
    Brian S Zuckerbraun
    Department of Surgery, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Shock 23:527-32. 2005
    ..The precise cellular mechanisms involved require further elucidation. CO may prove to be an adjunctive therapy that could be instituted rapidly and with ease as an out-of-hospital therapeutic modality for severe blood loss after trauma...
  8. pmc High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity
    John Evankovich
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 285:39888-97. 2010
    ..Together, these findings suggest that decreased nuclear HDAC1 and HDAC4 activities in hepatocytes following liver I/R is a mechanism that promotes the hyperacetylation and subsequent release of HMGB1...
  9. pmc Role of toll-like receptors in changes in gene expression and NF-kappa B activation in mouse hepatocytes stimulated with lipopolysaccharide
    Shubing Liu
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Infect Immun 70:3433-42. 2002
    ..Thus, hepatocytes respond to nanogram concentrations of LPS through a TLR4 response pathway...
  10. pmc Complement factor 3 deficiency attenuates hemorrhagic shock-related hepatic injury and systemic inflammatory response syndrome
    Changchun Cai
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA
    Am J Physiol Regul Integr Comp Physiol 299:R1175-82. 2010
    ..Our data indicate that complement activation contributes to inflammatory pathways and liver damage in HS/T. This suggests that targeting complement activation in the setting of severe injury could be useful...
  11. ncbi request reprint Carbon monoxide inhibits T lymphocyte proliferation via caspase-dependent pathway
    Ruiping Song
    Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, 3459 5th Avenue, Pittsburgh, PA 15213, USA
    J Immunol 172:1220-6. 2004
    ....
  12. pmc The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 201:1135-43. 2005
    ..Together, these results demonstrate that HMGB1 is an early mediator of injury and inflammation in liver I/R and implicates TLR4 as one of the receptors that is involved in the process...
  13. ncbi request reprint Toll-like receptor-4 signaling mediates hepatic injury and systemic inflammation in hemorrhagic shock
    Jose M Prince
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Am Coll Surg 202:407-17. 2006
    ..We sought to determine the role of lipolysaccharide through use of CD14-/- mice...
  14. ncbi request reprint The role of initial trauma in the host's response to injury and hemorrhage: insights from a correlation of mathematical simulations and hepatic transcriptomic analysis
    Claudio E Lagoa
    Department of Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Shock 26:592-600. 2006
    ..Mathematical simulations and DNA microarrays, both systems biology tools, may provide valuable insight into the complex global physiological interactions that occur in response to trauma and hemorrhagic shock...
  15. ncbi request reprint Peroxisomal localization of inducible nitric oxide synthase in hepatocytes
    Donna Beer Stolz
    Department of Cell Biology and Physiology, University of Pittsburgh Medical School, Pittsburgh, PA 12561, USA
    Hepatology 36:81-93. 2002
    ..In conclusion, these studies establish the peroxisome as a site of iNOS localization in hepatocytes and show a relationship between iNOS up-regulation and decreased expression of catalase...
  16. pmc Hepatocyte-specific high-mobility group box 1 deletion worsens the injury in liver ischemia/reperfusion: a role for intracellular high-mobility group box 1 in cellular protection
    Hai Huang
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
    Hepatology 59:1984-97. 2014
    ..Increased nuclear instability led to a resultant increase in the release of histones with subsequently more inflammatory cytokine production and organ damage through activation of Toll-like receptor 9...
  17. pmc Endogenous histones function as alarmins in sterile inflammatory liver injury through Toll-like receptor 9 in mice
    Hai Huang
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 2582, USA
    Hepatology 54:999-1008. 2011
    ..Conclusion: These novel findings reveal that histones represent a new class of DAMP molecules and serve as a crucial link between initial damage and activation of innate immunity during sterile inflammation...
  18. pmc Hemorrhagic shock augments lung endothelial cell activation: role of temporal alterations of TLR4 and TLR2
    Yuehua Li
    Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Am J Physiol Regul Integr Comp Physiol 297:R1670-80. 2009
    ....
  19. pmc Expression and subcellular localization of BNIP3 in hypoxic hepatocytes and liver stress
    Mallikarjuna R Metukuri
    Department of Surgery, Center for Biologic Imaging, University of Pittsburgh School of Medicine, W943 Biomedical Sciences Tower, 200 Lothrop St, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 296:G499-509. 2009
    ..In turn, the upregulation of BNIP3 appears to be one mechanism of hepatocyte cell death and liver damage in these settings...
  20. pmc In silico and in vivo approach to elucidate the inflammatory complexity of CD14-deficient mice
    Jose M Prince
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Mol Med 12:88-96. 2006
    ....
  21. pmc Anti-HMGB1 neutralizing antibody ameliorates gut barrier dysfunction and improves survival after hemorrhagic shock
    Runkuan Yang
    Department of Critical Care Medicine, University of Pittsburgh School of Medicine, PA 15621, USA
    Mol Med 12:105-14. 2006
    ..These data support the notion that HMGB1 is a mediator of HS/R-induced gut barrier dysfunction and suggest that anti-HMGB1 antibodies warrant further evaluation as a therapeutic to ameliorate the morbidity of HS/R in trauma patients...
  22. ncbi request reprint A nitric oxide scavenger protects against pulmonary inflammation following hemorrhagic shock
    Christian Hierholzer
    Department of Surgery, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pennsylvania 15213, USA
    Shock 17:98-103. 2002
    ..These data indicate that NOX prevents lung injury in this HS model, possibly through downmodulation of proinflammatory signaling and the shock-induced inflammatory response...
  23. ncbi request reprint Cutting edge: high-mobility group box 1 preconditioning protects against liver ischemia-reperfusion injury
    Kunihiko Izuishi
    Department of Surgery, University of Pittsburgh, PA 15213, USA
    J Immunol 176:7154-8. 2006
    ..Our studies demonstrate that in contrast to the role of HMGB1 as an early mediator of inflammation and organ damage in hepatic I/R, HMGB1 preconditioning can be protective...
  24. doi request reprint Changes in FADD levels, distribution, and phosphorylation in TNFalpha-induced apoptosis in hepatocytes is caspase-3, caspase-8 and BID dependent
    Xiaoying Zhang
    Department of Surgery, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA
    Apoptosis 13:983-92. 2008
    ..Changes in FADD levels and distribution may represent a novel feed-forward mechanism to propagate apoptosis signaling in hepatocytes...
  25. pmc Nitric oxide and thioredoxin type 1 modulate the activity of caspase 8 in HepG2 cells
    Rajib Sengupta
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Biochem Biophys Res Commun 391:1127-30. 2010
    ..The data obtained suggest that extrinsic apoptosis can be subjected to redox regulation before induction of proteolytic damage by caspase 3...
  26. ncbi request reprint Systemic inflammation and remote organ injury following trauma require HMGB1
    Ryan M Levy
    Dept of Surgery, F 1200 PUH, Univ of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15213, USA
    Am J Physiol Regul Integr Comp Physiol 293:R1538-44. 2007
    ..Collectively, these data demonstrate a critical role for a TLR4-HMGB1 pathway in the initiation of systemic inflammation and end-organ injury following isolated peripheral tissue injury...
  27. ncbi request reprint Regulation of tissue factor expression in smooth muscle cells with nitric oxide
    Melina R Kibbe
    Department of Surgery, A 1011, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    J Vasc Surg 37:650-9. 2003
    ..This study was undertaken to determine the effect of nitric oxide (NO) on tissue factor (TF) expression in vascular smooth muscle cells...
  28. doi request reprint A critical role for IFN regulatory factor 1 in NKT cell-mediated liver injury induced by alpha-galactosylceramide
    Zongxian Cao
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Immunol 185:2536-43. 2010
    ..Our findings revealed a novel mechanism of NKT cell-mediated liver injury in mice, which has implications in the development of human liver diseases...
  29. pmc Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14/TLR4/MD2-dependent uptake of lipopolysaccharide by hepatocytes
    Melanie J Scott
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 283:29433-46. 2008
    ..However, TLR4/MD2 remain essential components at the cell surface as part of the LPS receptor complex. We therefore suggest novel roles for TLR4/MD2, CD11b/CD18, TIRAP, and p38 MAPK in LPS uptake by hepatocytes...
  30. ncbi request reprint Carbon monoxide protects hepatocytes from TNF-alpha/Actinomycin D by inhibition of the caspase-8-mediated apoptotic pathway
    Hoe Suk Kim
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Biochem Biophys Res Commun 344:1172-8. 2006
    ..These data indicate that CO interferes with apoptotic signaling at a proximal step...
  31. ncbi request reprint Systemic inflammation and remote organ damage following bilateral femur fracture requires Toll-like receptor 4
    Ryan M Levy
    Department of Surgery, F 1200 PUH, University of Pittsburgh, 200 Lothrop St, Pittsburgh, PA 15217, USA
    Am J Physiol Regul Integr Comp Physiol 291:R970-6. 2006
    ..Application of these findings in an evolutionary context suggests that multicellular organisms have evolved to use the same pattern recognition receptor for surviving traumatic and infectious challenges...
  32. ncbi request reprint Hypoxia activates c-Jun N-terminal kinase via Rac1-dependent reactive oxygen species production in hepatocytes
    Kevin P Mollen
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Shock 28:270-7. 2007
    ..Together, these data suggest that ROS generation during hypoxia in the liver directly leads to JNK activation in a Rac1-dependent process...
  33. ncbi request reprint Systemic inflammation and end organ damage following trauma involves functional TLR4 signaling in both bone marrow-derived cells and parenchymal cells
    Kevin P Mollen
    Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15217, USA
    J Leukoc Biol 83:80-8. 2008
    ..These data demonstrate that functional TLR4 is required in BM-derived cells and parenchymal cells for an optimal inflammatory response to trauma...
  34. ncbi request reprint Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury
    Allan Tsung
    Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Presbyterian Hospital F1200, Pittsburgh, PA 15213, USA
    J Leukoc Biol 81:119-28. 2007
    ..It thus appears that functional TLR4 on DC is required for I/R-induced injury. Furthermore, HMGB1 may direct the inflammatory responses mediated by DC, at least in part, by enhancing TLR4 expression and reactivity to it and other DAMPs...
  35. ncbi request reprint Thioredoxin catalyzes the denitrosation of low-molecular mass and protein S-nitrosothiols
    Rajib Sengupta
    Department of Surgery, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Biochemistry 46:8472-83. 2007
    ..The data obtained are discussed within the general reaction mechanisms encompassing the cellular homeostasis of S-nitrosothiols...
  36. ncbi request reprint Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: role of HMGB1-TLR4 signaling
    Jie Fan
    Department of Surgery, School of Medicine, University of Pittsburgh, and Division of Pediatric Surgery, Children s Hospital of Pittsburgh, PA 15213, USA
    J Immunol 178:6573-80. 2007
    ..Thus, PMN NAD(P)H oxidase activation, induced by HS/R and as mediated by HMGB1/TLR4 signaling, is an important mechanism responsible for PMN-mediated inflammation and organ injury after hemorrhage...
  37. ncbi request reprint Hepatic ischemia/reperfusion injury involves functional TLR4 signaling in nonparenchymal cells
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Immunol 175:7661-8. 2005
    ..Together, these results demonstrate that TLR4 engagement on actively phagocytic nonparenchymal cells such as Kupffer cells is required for warm I/R-induced injury and inflammation in the liver...
  38. ncbi request reprint The acute inflammatory response in diverse shock states
    Carson C Chow
    Department of Mathematics, University of Pittsburgh, Pittsburgh, Pensylvania 15261, USA
    Shock 24:74-84. 2005
    ....
  39. ncbi request reprint A DNA microarray study of nitric oxide-induced genes in mouse hepatocytes: implications for hepatic heme oxygenase-1 expression in ischemia/reperfusion
    Ruben Zamora
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Nitric Oxide 7:165-86. 2002
    ....
  40. ncbi request reprint Induced nitric oxide promotes intestinal inflammation following hemorrhagic shock
    Christian Hierholzer
    Department of Surgery, University of Pittsburgh Medical Center, F1264 200 Lothrop St, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 286:G225-33. 2004
    ....
  41. pmc Linking oxidative stress to inflammation: Toll-like receptors
    Roop Gill
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Free Radic Biol Med 48:1121-32. 2010
    ..Finally, potential mechanisms by which reactive oxygen species from NADPH oxidase can signal the commencement of inflammatory pathways through TLRs are explored...
  42. ncbi request reprint Cisplatin prevents high mobility group box 1 release and is protective in a murine model of hepatic ischemia/reperfusion injury
    Jon Cardinal
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Hepatology 50:565-74. 2009
    ....
  43. doi request reprint Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction
    Atsunori Nakao
    Department of Surgery, University of Pittsburgh Medical Center, E1551 BST, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Biochem Biophys Res Commun 367:674-9. 2008
    ..This pharmacological action of galantamine may, at least in part, account for the superior clinical efficacy of galantamine in vascular dementia and Alzheimer disease...
  44. pmc Carbon monoxide decreases the level of iNOS protein and active dimer in IL-1beta-stimulated hepatocytes
    Hoe Suk Kim
    Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Presbyterian Hospital F1200, Pittsburgh, PA 15213, USA
    Nitric Oxide 18:256-65. 2008
    ..Our results imply that CO exposure decreases NO production by suppressing dimer formation and increasing iNOS degradation through a process involving p38 activation...
  45. doi request reprint Carbon monoxide activates NF-kappaB via ROS generation and Akt pathways to protect against cell death of hepatocytes
    Hoe Suk Kim
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 295:G146-G152. 2008
    ..This pathway may prove to be important in maintenance of hepatic function in both physiological and pathophysiological conditions...
  46. ncbi request reprint Autologous nitric oxide protects mouse and human keratinocytes from ultraviolet B radiation-induced apoptosis
    Richard Weller
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Am J Physiol Cell Physiol 284:C1140-8. 2003
    ..These results demonstrate an antiapoptotic role for NO in keratinocytes, mediated by cGMP, and indicate an antiapoptotic role for both eNOS and iNOS in skin damage induced by UVB...
  47. pmc Calcium/calmodulin-dependent protein kinase (CaMK) IV mediates nucleocytoplasmic shuttling and release of HMGB1 during lipopolysaccharide stimulation of macrophages
    Xianghong Zhang
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Immunol 181:5015-23. 2008
    ..Collectively, our results demonstrate that CaMKIV promotes the nucleocytoplasmic shuttling of HMGB1 and suggest that the process may be mediated through CaMKIV-dependent serine phosphorylation of HMGB1...
  48. pmc Endotoxin uptake in mouse liver is blocked by endotoxin pretreatment through a suppressor of cytokine signaling-1-dependent mechanism
    Melanie J Scott
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Hepatology 49:1695-708. 2009
    ..LPS-induced SOCS1 upregulation increases degradation of TIRAP and prevents subsequent LPS uptake. The exploitation of these mechanisms of LPS desensitization in the liver may be important in future sepsis therapies...
  49. ncbi request reprint The modulation of hepatic injury and heat shock expression by inhibition of inducible nitric oxide synthase after hemorrhagic shock
    John M Menezes
    Department of Surgery, University of Pittsburgh, Pennsylvania 15213, USA
    Shock 17:13-8. 2002
    ..We conclude that excessive NO production from iNOS contributes to shock-induced hepatic injury. Our data suggest HSP expression may reflect the degree of ischemic injury after hemorrhage...
  50. doi request reprint Low-dose cisplatin administration in murine cecal ligation and puncture prevents the systemic release of HMGB1 and attenuates lethality
    Pinhua Pan
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Leukoc Biol 86:625-32. 2009
    ..Platinating agents in general and Cis specifically may be a novel approach to the treatment of sepsis...
  51. pmc Preactivation of NKT cells with alpha-GalCer protects against hepatic ischemia-reperfusion injury in mouse by a mechanism involving IL-13 and adenosine A2A receptor
    Zongxian Cao
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Am J Physiol Gastrointest Liver Physiol 297:G249-58. 2009
    ..These findings provide the first evidence that hepatic preconditioning by preactivation of NKT cells with alpha-GalCer protects the liver from IR injury via an IL-13 and adenosine A2AR-dependent mechanism...
  52. ncbi request reprint Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury
    Leo E Otterbein
    Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Montefiore University Hospital, Pittsburgh, Pennsylvania, USA
    Nat Med 9:183-90. 2003
    ..These findings demonstrate a protective role for CO in vascular injury and support its use as a therapeutic agent...
  53. ncbi request reprint The role of hepatic type 1 plasminogen activator inhibitor (PAI-1) during murine hemorrhagic shock
    Claudio E Lagoa
    Department of Surgery, University of Pittsburgh, S411 B South BST, Pittsburgh, PA 15261, USA
    Hepatology 42:390-9. 2005
    ..In conclusion, PAI-1 protein is a negative effector of hepatic damage after HS-R through its influence on classic regulators of hepatic growth, as opposed to its role in fibrinolysis...
  54. ncbi request reprint Hemorrhagic shock-activated neutrophils augment TLR4 signaling-induced TLR2 upregulation in alveolar macrophages: role in hemorrhage-primed lung inflammation
    Jie Fan
    Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15240, USA
    Am J Physiol Lung Cell Mol Physiol 290:L738-L746. 2006
    ..Thus TLR2 expression in AMphi, signaled by TLR4 and regulated by shock-activated PMN, is an important positive-feedback mechanism responsible for shock-primed PMN infiltration into the lung after primary PMN sequestration...
  55. ncbi request reprint The role of RAGE in the pathogenesis of intestinal barrier dysfunction after hemorrhagic shock
    Kathleen G Raman
    Univ of Pittsburgh School of Medicine, 616 Scaife Hall, 3550 Terrace St, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 291:G556-65. 2006
    ..Circulating IL-10 levels were higher in rage(-/-) compared with rage(+/+) mice. These results suggest that activation of RAGE-dependent signaling is a key factor leading to gut mucosal barrier dysfunction after HS/R...
  56. ncbi request reprint Inflammatory modulation of hepatocyte apoptosis by nitric oxide: in vivo, in vitro, and in silico studies
    Yoram Vodovotz
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Curr Mol Med 4:753-62. 2004
    ..Our studies suggest that modulation of iron, oxygen, and superoxide may dictate whether NO* is hepatoprotective or hepatotoxic...
  57. ncbi request reprint Patterns of cytokine release and evolution of remote organ dysfunction after bilateral femur fracture
    Philipp Kobbe
    Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Shock 30:43-7. 2008
    ....
  58. ncbi request reprint Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments
    Marina V Kameneva
    McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh, 3025 East Carson Street, Pittsburgh, PA 15203, USA
    Biorheology 41:53-64. 2004
    ..Our findings suggest that the drag-reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders...
  59. pmc An adequately robust early TNF-alpha response is a hallmark of survival following trauma/hemorrhage
    Rajaie Namas
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    PLoS ONE 4:e8406. 2009
    ..Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considered detrimental...
  60. doi request reprint Fresh frozen plasma is independently associated with a higher risk of multiple organ failure and acute respiratory distress syndrome
    Gregory A Watson
    Division of General Surgery and Trauma, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
    J Trauma 67:221-7; discussion 228-30. 2009
    ..We hypothesized that plasma-rich transfusion components would be independently associated with a lower risk of mortality but result in a greater risk of morbid complications...
  61. ncbi request reprint Orally administered nitrite attenuates cardiac allograft rejection in rats
    Jianghua Zhan
    Department of Surgery, Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
    Surgery 146:155-65. 2009
    ..Recent studies have shown that nitrite serves as an endogenous reservoir of nitric oxide (NO), particularly in the presence of hypoxia and ischemia. We hypothesized that exogenous nitrite supplementation would protect cardiac allografts...
  62. ncbi request reprint Emerging paradigm: toll-like receptor 4-sentinel for the detection of tissue damage
    Kevin P Mollen
    Department of Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Shock 26:430-7. 2006
    ..This review will detail the observations implicating a TLR family member, TLR4, as a key component of the initial injury response...
  63. ncbi request reprint Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species
    Brian S Zuckerbraun
    Department of Surgery, University of Pittsburgh School of Medicine, NW653 MUH, 3459 Fifth Ave, Pittsburgh, PA 15213, USA
    FASEB J 21:1099-106. 2007
    ....
  64. doi request reprint Local exposure of bone components to injured soft tissue induces Toll-like receptor 4-dependent systemic inflammation with acute lung injury
    Philipp Kobbe
    Department of Orthopaedic Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Shock 30:686-91. 2008
    ..These findings suggest that bone components contribute to systemic inflammation and acute lung injury after long bone fractures via TLR-4 signaling and support the notion of a central role for TLR-4 in sensing tissue damage...
  65. pmc Hepatocytes express functional NOD1 and NOD2 receptors: a role for NOD1 in hepatocyte CC and CXC chemokine production
    Melanie J Scott
    Department of Surgery, University of Pittsburgh School of Medicine, NW 607 MUH, 3459 Fifth Ave, Pittsburgh, PA 15213, USA
    J Hepatol 53:693-701. 2010
    ..Both NOD1 and NOD2 have been associated with many inflammatory diseases, although their role in liver inflammation and infection has not been well studied...
  66. ncbi request reprint Role of nitric oxide in liver injury
    Tracy Chen
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Curr Mol Med 3:519-26. 2003
    ..The purpose of this paper is to review the current understanding of the role of NO in liver injury...
  67. ncbi request reprint Nitric oxide-mediated inhibition of caspase-dependent T lymphocyte proliferation
    Raja S Mahidhara
    Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA
    J Leukoc Biol 74:403-11. 2003
    ..Previous studies demonstrated inhibition of apoptosis through S-nitrosylation of caspases; the present studies extend this effect to inhibition of caspase-dependent T cell proliferation...
  68. pmc Incidental radiographic findings after injury: dedicated attention results in improved capture, documentation, and management
    Jason L Sperry
    Division of General Surgery and Trauma, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
    Surgery 148:618-24. 2010
    ..We hypothesized a dedicated incidental finding coordinator would increase incidental finding capture and promote notification, follow-up, and documentation of incidental finding events...
  69. ncbi request reprint The Department of Surgery at the School of Medicine at the University Of Pittsburgh, Pittsburgh, Pa
    Timothy R Billiar
    Department of Surgery, Presbyterian University Hospital, Pittsburgh, PA 15213, USA
    Arch Surg 139:466-8. 2004
  70. ncbi request reprint Thioredoxin and lipoic acid catalyze the denitrosation of low molecular weight and protein S-nitrosothiols
    Detcho A Stoyanovsky
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Am Chem Soc 127:15815-23. 2005
    ..We conclude that both thioredoxin and dihydrolipoic acid may be involved in the regulation of cellular S-nitrosothiols...
  71. ncbi request reprint The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity
    Michael T Lotze
    Department of Surgery, G 27A Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
    Immunol Rev 220:60-81. 2007
    ....
  72. ncbi request reprint Masquerader: high mobility group box-1 and cancer
    Jessica E Ellerman
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Clin Cancer Res 13:2836-48. 2007
    ..This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy...
  73. ncbi request reprint Nitric oxide prevents 6-hydroxydopamine-induced apoptosis in PC12 cells through cGMP-dependent PI3 kinase/Akt activation
    Kwon Soo Ha
    Vascular System Research Center and Department of Molecular and Cellular Biochemistry, Kangwon National University, School of Medicine, Chunchon, Kangwon Do, Korea
    FASEB J 17:1036-47. 2003
    ..Our data suggest that the NO/cGMP pathway suppresses 6-OHDA-induced PC12 cell apoptosis by suppressing the mitochondrial apoptosis signal via PKG/PI3K/Akt-dependent Bad phosphorylation...
  74. ncbi request reprint Neuronal NOS-mediated nitration and inactivation of manganese superoxide dismutase in brain after experimental and human brain injury
    Hulya Bayir
    Safar Center for Resuscitation Research, Pittsburgh, Pennsylvania 15260, USA
    J Neurochem 101:168-81. 2007
    ..Nitration and inactivation of MnSOD could lead to self-amplification of oxidative stress in the brain progressively enhancing peroxynitrite production and secondary damage...
  75. ncbi request reprint Tissue hypoxia activates JNK in the liver during hemorrhagic shock
    Carol A McCloskey
    Department of General Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15260, USA
    Shock 22:380-6. 2004
    ..These results identify tissue hypoxia as a key factor in activating early signaling events in the liver following hemorrhage, as measured by JNK phosphorylation...
  76. ncbi request reprint Signaling and function of caspase and c-jun N-terminal kinase in cisplatin-induced apoptosis
    Myoung Sook Koo
    Vascular System Research Center, Kangwon National University, Chunchon, Korea
    Mol Cells 13:194-201. 2002
    ..These data suggest that the cisplatin-induced apoptotic signal is initiated by the caspase-8-independent cytochrome c release, and the JNK activation protects cells from cisplatin-induced apoptosis via the metallothionein expression...
  77. ncbi request reprint Ultraviolet irradiation increases FADD protein in apoptotic human keratinocytes
    Peter K M Kim
    Department of Surgery, University of Pittsburgh Medical Center, NW607 MUH, Pittsburgh, PA 15213, USA
    Biochem Biophys Res Commun 302:290-5. 2003
    ..Inhibition of FADD protein by adenoviral expression of anti-sense FADD reduced keratinocyte apoptosis. Regulation of FADD expression by UV may serve to enhance death receptor-mediated keratinocyte death...
  78. ncbi request reprint Requirements for NF-kappaB activation in hemorrhagic shock
    Christian Hierholzer
    Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universitat Munchen, Germany
    Arch Orthop Trauma Surg 122:44-7. 2002
    ..Thus, NF-kappaB activation requires both phases of HS, occurs rapidly following resuscitation, and persists throughout the early stages of dysfunctional inflammation following resuscitation...
  79. ncbi request reprint Potentiation of nitric oxide-induced apoptosis in p53-/- vascular smooth muscle cells
    Melina R Kibbe
    Department of Surgery, University of Pittsburgh, 677 Scaife Hall, Pittsburgh, PA 15261, USA
    Am J Physiol Cell Physiol 282:C625-34. 2002
    ..Inhibition of p38 MAPK with SB-203580 or of MEK1/2 with PD-98059 blocked NO-induced apoptosis. Therefore, p53 may protect VSMC against NO-mediated apoptosis, in part, through differential regulation of MAPK pathways...
  80. ncbi request reprint Hypoxia inhibition of apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
    Sang Youel Park
    Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Biochem Biophys Res Commun 291:150-3. 2002
    ..Our findings suggest that an increase of antiapoptotic proteins induced by hypoxia may regulate the therapeutic activity of TRAIL protein in cancer therapy...
  81. ncbi request reprint Nitric oxide suppresses inducible nitric oxide synthase expression by inhibiting post-translational modification of IkappaB
    Kwang Chang
    Department of Molecular and Cellular Biochemistry, School of Medicine Kangwon National University, Chuncheon, Gangwon Do, Korea
    Exp Mol Med 36:311-24. 2004
    ..These results identify a novel negative feedback mechanism whereby NO down-regulates iNOS gene expression...
  82. ncbi request reprint Making progress in an enlightened era: opportunities and obstacles
    Timothy R Billiar
    Presbyterian University Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    Surg Infect (Larchmt) 8:5-14. 2007
  83. doi request reprint Male gender is associated with excessive IL-6 expression following severe injury
    Jason L Sperry
    Division of Trauma and General Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    J Trauma 64:572-8; discussion 578-9. 2008
    ....
  84. ncbi request reprint Ischemic preconditioning of the murine liver protects through the Akt kinase pathway
    Kunihiko Izuishi
    First Department of Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
    Hepatology 44:573-80. 2006
    ..Modulation of this pathway may be a potential strategy in clinical settings of ischemic liver injury to decrease organ damage...
  85. ncbi request reprint In silico models of acute inflammation in animals
    Yoram Vodovotz
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Shock 26:235-44. 2006
    ..Mathematical modeling may provide insights into the complex dynamics of acute inflammation in a manner that can be tested in vivo using many fewer animals than has been possible previously...
  86. ncbi request reprint Fas-associating death domain protein overexpression induces apoptosis in lung cancer cells
    Peter K M Kim
    Department of Surgery Laboratories, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Thorac Cardiovasc Surg 125:1336-42. 2003
    ..We hypothesized that overexpression of Fas-associating death domain protein would effectively eradicate lung cancer cells by induction of apoptosis...
  87. ncbi request reprint Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury: support for a neuroprotective role of iNOS
    Hulya Bayir
    Safar Center for Resuscitation Research, University of Pittsburgh Medical Center, Pennslyvania 15260, USA
    J Cereb Blood Flow Metab 25:673-84. 2005
    ..iNOS also contributes protein nitrosylation and nitration. Colocalization of 3NT with macrophages and MPO suggests generation of nitrating agents by macrophages and/or phagocytosis of nitrated proteins...
  88. pmc Carbon monoxide reverses established pulmonary hypertension
    Brian S Zuckerbraun
    Department of Surgery Transplant Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Exp Med 203:2109-19. 2006
    ..In conclusion, these data demonstrate that CO reverses established PAH dependent on NO generation supporting the use of CO clinically to treat pulmonary hypertension...
  89. pmc Intra-abdominal activation of a local inflammatory response within the human muscularis externa during laparotomy
    Jorg C Kalff
    Department of Medicine, University of Pittsburgh, Pennsylvania 15261, USA
    Ann Surg 237:301-15. 2003
    ..To investigate the initiation of a complex inflammatory response within the human intestinal muscularis intraoperatively so as to determine the clinical applicability of the inflammatory hypothesis of postoperative ileus...
  90. ncbi request reprint RhoA influences the nuclear localization of extracellular signal-regulated kinases to modulate p21Waf/Cip1 expression
    Brian S Zuckerbraun
    University of Pittsburgh, Department of Surgery, Pittsburgh, PA, USA
    Circulation 108:876-81. 2003
    ..The purpose of this investigation was to examine whether RhoA regulates ERK downstream signaling and cellular proliferation through its effects on the cytoskeleton and the nuclear localization of ERK...
  91. pmc Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance
    RAJESH K ANEJA
    Department of Critical Care Medicine and Pediatrics, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    J Leukoc Biol 84:1326-34. 2008
    ..Taken together, these results suggest that extracellular HMGB1 induces LPS tolerance, and the RAGE receptor is required for this induction...
  92. ncbi request reprint Nitric oxide (NO) pretreatment increases cytokine-induced NO production in cultured rat hepatocytes by suppressing GTP cyclohydrolase I feedback inhibitory protein level and promoting inducible NO synthase dimerization
    Joon Hong Park
    Vascular System Research Center and Department of Molecular and Cellular Biochemistry, Kangwon National University, School of Medicine, Chunchon, Kangwon Do 200 701, Korea
    J Biol Chem 277:47073-9. 2002
    ..These results suggest that SNAP pretreatment increased NO production from iNOS by elevating cellular BH(4) levels and promoting iNOS subunit dimerization through the suppression of GFRP levels and subsequent activation of GTPCHI...

Research Grants29

  1. NITRIC OXIDE AND HEPATIC FUNCTION IN SEPSIS AND TRAUMA
    Timothy Billiar; Fiscal Year: 2001
    ..By defining the protective mechanisms in hepatocytes, we will gain insights into the molecular mechanisms that lead to cellular toxicity in sepsis in susceptible organs. ..
  2. TRAINING IN TRAUMA AND SEPSIS RESEARCH
    Timothy Billiar; Fiscal Year: 2007
    ..All the training can be carried out in the more than 50,000 sq ft of fully equipped lab space available. ..
  3. NITRIC OXIDE AND HEPATIC FUNCTION IN SEPSIS AND TRAUMA
    Timothy Billiar; Fiscal Year: 2002
    ..By defining the protective mechanisms in hepatocytes, we will gain insights into the molecular mechanisms that lead to cellular toxicity in sepsis in susceptible organs. ..
  4. POSTTRAUMATIC SEPSIS--REGULATION OF LPS BINDING PROTEIN
    Timothy Billiar; Fiscal Year: 1999
    ..They believe their results should yield key insights into strategies utilized by the host to respond to microbial invasion and the mechanisms leading to excessive activation of inflammatory mediator cascades. ..
  5. NITRIC OXIDE AND HEPATIC FUNCTION IN SEPSIS AND TRAUMA
    Timothy Billiar; Fiscal Year: 1999
    ..By defining the protective mechanisms in hepatocytes, we will gain insights into the molecular mechanisms that lead to cellular toxicity in sepsis in susceptible organs. ..
  6. Post-Traumatic Sepsis: Regulation of LPS Binding Protein
    Timothy Billiar; Fiscal Year: 2007
    ..Insights gained from these studies should significantly enhance our evolving understanding of the common responses of the liver to sudden disruptions of homeostasis, both from pathogens and from damaged tissue. ..
  7. POSTTRAUMATIC SEPSIS--REGULATION OF LPS BINDING PROTEIN
    Timothy Billiar; Fiscal Year: 2000
    ..They believe their results should yield key insights into strategies utilized by the host to respond to microbial invasion and the mechanisms leading to excessive activation of inflammatory mediator cascades. ..
  8. NITRIC OXIDE AND HEPATIC FUNCTION IN SEPSIS AND TRAUMA
    Timothy Billiar; Fiscal Year: 2007
    ..abstract_text> ..
  9. Post-Traumatic Sepsis: Regulation of LPS Binding Protein
    Timothy Billiar; Fiscal Year: 2009
    ..Insights gained from these studies should significantly enhance our evolving understanding of the common responses of the liver to sudden disruptions of homeostasis, both from pathogens and from damaged tissue. ..
  10. Post-Traumatic Sepsis: Regulation of LPS Binding Protein
    Timothy Billiar; Fiscal Year: 2005
    ..Insights gained from these studies should significantly enhance our understanding of the earliest events in host-microbe interactions in surgical sepsis. ..
  11. Post-Traumatic Sepsis: Regulation of LPS Binding Protein
    Timothy Billiar; Fiscal Year: 2004
    ..Insights gained from these studies should significantly enhance our understanding of the earliest events in host-microbe interactions in surgical sepsis. ..
  12. Post-Traumatic Sepsis: Regulation of LPS Binding Protein
    Timothy Billiar; Fiscal Year: 2003
    ..Insights gained from these studies should significantly enhance our understanding of the earliest events in host-microbe interactions in surgical sepsis. ..
  13. Post-Traumatic Sepsis: Regulation of LPS Binding Protein
    Timothy Billiar; Fiscal Year: 2002
    ..Insights gained from these studies should significantly enhance our understanding of the earliest events in host-microbe interactions in surgical sepsis. ..
  14. POSTTRAUMATIC SEPSIS--REGULATION OF LPS BINDING PROTEIN
    Timothy Billiar; Fiscal Year: 2001
    ..They believe their results should yield key insights into strategies utilized by the host to respond to microbial invasion and the mechanisms leading to excessive activation of inflammatory mediator cascades. ..
  15. NITRIC OXIDE AND HEPATIC FUNCTION IN SEPSIS AND TRAUMA
    Timothy Billiar; Fiscal Year: 2000
    ..By defining the protective mechanisms in hepatocytes, we will gain insights into the molecular mechanisms that lead to cellular toxicity in sepsis in susceptible organs. ..
  16. Post-Traumatic Sepsis: Regulation of LPS Binding Protein
    Timothy R Billiar; Fiscal Year: 2010
    ..Insights gained from these studies should significantly enhance our evolving understanding of the common responses of the liver to sudden disruptions of homeostasis, both from pathogens and from damaged tissue. ..