interleukin 8b receptors


Summary: High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and T-LYMPHOCYTES. These receptors also bind several other CXC CHEMOKINES.

Top Publications

  1. Gorio A, Madaschi L, Zadra G, Marfia G, Cavalieri B, Bertini R, et al. Reparixin, an inhibitor of CXCR2 function, attenuates inflammatory responses and promotes recovery of function after traumatic lesion to the spinal cord. J Pharmacol Exp Ther. 2007;322:973-81 pubmed
    ..Methylprednisolone was used as a reference drug; such treatment reduced cytokine production but failed to affect the rate of hind limb recovery. ..
  2. Maxwell P, Gallagher R, Seaton A, Wilson C, Scullin P, Pettigrew J, et al. HIF-1 and NF-kappaB-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells. Oncogene. 2007;26:7333-45 pubmed
    ..These results suggest that IL-8 signaling confers a survival advantage to hypoxic prostate cancer cells, and therefore, strategies to inhibit IL-8 signaling may sensitize hypoxic tumor cells to conventional treatments. ..
  3. Popivanova B, Koike K, Tonchev A, Ishida Y, Kondo T, Ogawa S, et al. Accumulation of microglial cells expressing ELR motif-positive CXC chemokines and their receptor CXCR2 in monkey hippocampus after ischemia-reperfusion. Brain Res. 2003;970:195-204 pubmed
  4. Seaton A, Scullin P, Maxwell P, Wilson C, Pettigrew J, Gallagher R, et al. Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis. 2008;29:1148-56 pubmed publisher
    ..In addition, our data show that IL-8-promoted regulation of the AR attenuates the effectiveness of the AR antagonist bicalutamide in reducing CaP cell viability. ..
  5. Smithson A, Sarrias M, Barcelo J, Suarez B, Horcajada J, Soto S, et al. Expression of interleukin-8 receptors (CXCR1 and CXCR2) in premenopausal women with recurrent urinary tract infections. Clin Diagn Lab Immunol. 2005;12:1358-63 pubmed
    ..These results suggest that a low level of CXCR2 expression may increase the susceptibilities of premenopausal women to urinary tract infections. ..
  6. Belperio J, Keane M, Burdick M, Gomperts B, Xue Y, Hong K, et al. CXCR2/CXCR2 ligand biology during lung transplant ischemia-reperfusion injury. J Immunol. 2005;175:6931-9 pubmed
  7. Martin C, Burdon P, Bridger G, Gutierrez Ramos J, Williams T, Rankin S. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity. 2003;19:583-93 pubmed
  8. Padovani Claudio D, Liu L, Ransohoff R, Miller R. Alterations in the oligodendrocyte lineage, myelin, and white matter in adult mice lacking the chemokine receptor CXCR2. Glia. 2006;54:471-83 pubmed
    ..Together, these findings indicate that the chemokine receptor CXCR2 is important for the development and maintenance of the oligodendrocyte lineage, myelination, and white matter in the vertebrate CNS. ..
  9. Murphy C, McGurk M, Pettigrew J, Santinelli A, Mazzucchelli R, Johnston P, et al. Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer. Clin Cancer Res. 2005;11:4117-27 pubmed

More Information


  1. Liu L, Belkadi A, Darnall L, Hu T, Drescher C, Cotleur A, et al. CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis. Nat Neurosci. 2010;13:319-26 pubmed publisher
    ..These data suggest that cuprizone-induced demyelination is useful for modeling certain aspects of multiple sclerosis pathogenesis. ..
  2. Nasser M, Raghuwanshi S, Grant D, Jala V, Rajarathnam K, Richardson R. Differential activation and regulation of CXCR1 and CXCR2 by CXCL8 monomer and dimer. J Immunol. 2009;183:3425-32 pubmed publisher
    ..These distinct properties of the ligand and the receptors play a critical role in orchestrating neutrophil recruitment and eliciting cytotoxic activity during an inflammatory response. ..
  3. Varney M, Li A, Dave B, Bucana C, Johansson S, Singh R. Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different metastatic potential and their role in interleukin-8 (CXCL-8)-mediated modulation of metastatic phenotype. Clin Exp Metastasis. 2003;20:723-31 pubmed
    ..In summary, the data suggest that constitutive expression of CXCR1 and CXCR2 play an important role regulating the IL-8-mediated metastatic phenotype in human malignant melanoma cells. ..
  4. Li A, Dubey S, Varney M, Dave B, Singh R. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol. 2003;170:3369-76 pubmed
    ..Our data suggest that IL-8 directly enhanced endothelial cell proliferation, survival, and MMP expression in CXCR1- and CXCR2-expressing endothelial cells and regulated angiogenesis. ..
  5. Trettel F, Di Bartolomeo S, Lauro C, Catalano M, Ciotti M, Limatola C. Ligand-independent CXCR2 dimerization. J Biol Chem. 2003;278:40980-8 pubmed
    ..Taken together, we conclude from these studies that CXCR2 functions as a dimer and that truncated receptors negatively modulate receptor activities competing for the formation of wt/wt dimers. ..
  6. Varney M, Johansson S, Singh R. Distinct expression of CXCL8 and its receptors CXCR1 and CXCR2 and their association with vessel density and aggressiveness in malignant melanoma. Am J Clin Pathol. 2006;125:209-16 pubmed
    ..Consistent with the transition from radial to vertical growth phase melanoma, expression of CXCL8 and its receptor, CXCR2, may be key in the switch to an aggressive, more metastatic phenotype. ..
  7. Omari K, John G, Sealfon S, Raine C. CXC chemokine receptors on human oligodendrocytes: implications for multiple sclerosis. Brain. 2005;128:1003-15 pubmed
  8. Prado G, Suetomi K, Shumate D, Maxwell C, Ravindran A, Rajarathnam K, et al. Chemokine signaling specificity: essential role for the N-terminal domain of chemokine receptors. Biochemistry. 2007;46:8961-8 pubmed
    ..Thus, the diversity and intensity of inflammatory and noninflammatory responses mediated by chemokine receptors appear to be primarily determined by the initial interaction between the receptor N-terminus and the N-loop of chemokines. ..
  9. Danik M, Puma C, Quirion R, Williams S. Widely expressed transcripts for chemokine receptor CXCR1 in identified glutamatergic, gamma-aminobutyric acidergic, and cholinergic neurons and astrocytes of the rat brain: a single-cell reverse transcription-multiplex polymerase chain reaction stud. J Neurosci Res. 2003;74:286-95 pubmed
    ..This is the first study to demonstrate the widespread expression of CXCR1 transcripts in the brain and suggests that CXCR1 may have hitherto unsuspected roles in neuromodulation and inflammation. ..
  10. Vall├Ęs A, Grijpink Ongering L, de Bree F, Tuinstra T, Ronken E. Differential regulation of the CXCR2 chemokine network in rat brain trauma: implications for neuroimmune interactions and neuronal survival. Neurobiol Dis. 2006;22:312-22 pubmed
  11. Donahue T, Hines O. CXCR2 and RET single nucleotide polymorphisms in pancreatic cancer. World J Surg. 2009;33:710-5 pubmed publisher
  12. Wilson S, Wilkinson G, Milligan G. The CXCR1 and CXCR2 receptors form constitutive homo- and heterodimers selectively and with equal apparent affinities. J Biol Chem. 2005;280:28663-74 pubmed
    ..Di Bartolomeo, S., Lauro, C., Catalano, M., Ciotti, M. T., and Limatola, C. (2003) J. Biol. Chem. 278, 40980-40988). ..
  13. Londhe V, Belperio J, Keane M, Burdick M, Xue Y, Strieter R. CXCR2/CXCR2 ligand biological axis impairs alveologenesis during dsRNA-induced lung inflammation in mice. Pediatr Res. 2005;58:919-26 pubmed
    ..These findings demonstrate that the CXCR2/CXCR2 ligand biologic axis plays an important role during the pathogenesis of dsRNA-induced lung injury and decreased alveolization and may be relevant to the pathogenesis of BPD. ..
  14. Hosking M, Liu L, Ransohoff R, Lane T. A protective role for ELR+ chemokines during acute viral encephalomyelitis. PLoS Pathog. 2009;5:e1000648 pubmed publisher
    ..Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS. ..
  15. Moepps B, Nuesseler E, Braun M, Gierschik P. A homolog of the human chemokine receptor CXCR1 is expressed in the mouse. Mol Immunol. 2006;43:897-914 pubmed
    ..These findings suggest that a homolog or ortholog of hCXCR1 is expressed in the mouse to be activated by a hitherto unknown CXC chemokine of the mouse. ..
  16. Rittner H, Labuz D, Schaefer M, Mousa S, Schulz S, Schafer M, et al. Pain control by CXCR2 ligands through Ca2+-regulated release of opioid peptides from polymorphonuclear cells. FASEB J. 2006;20:2627-9 pubmed
    ..These findings demonstrate that, beyond cell recruitment, CXCR2 ligands induce Ca2+-regulated opioid release from PMN and thereby inhibit inflammatory pain in vivo. ..
  17. Walters I, Austin C, Austin R, Bonnert R, Cage P, Christie M, et al. Evaluation of a series of bicyclic CXCR2 antagonists. Bioorg Med Chem Lett. 2008;18:798-803 pubmed
  18. Mestas J, Burdick M, Reckamp K, Pantuck A, Figlin R, Strieter R. The role of CXCR2/CXCR2 ligand biological axis in renal cell carcinoma. J Immunol. 2005;175:5351-7 pubmed
    ..These data support the notion that CXCR2/CXCR2 ligand biology is an important component of RCC tumor-associated angiogenesis and tumorigenesis. ..
  19. Smith M, Olson T, Ley K. CXCR2- and E-selectin-induced neutrophil arrest during inflammation in vivo. J Exp Med. 2004;200:935-9 pubmed
    ..These data show that E-selectin- and chemokine-mediated arrest mechanisms are overlapping in this model and identify CXCR2 as an important neutrophil arrest chemokine in vivo. ..
  20. Yanagawa J, Walser T, Zhu L, Hong L, Fishbein M, Mah V, et al. Snail promotes CXCR2 ligand-dependent tumor progression in non-small cell lung carcinoma. Clin Cancer Res. 2009;15:6820-9 pubmed publisher
    ..Snail upregulation plays a role in human NSCLC by promoting tumor progression mediated by CXCR2 ligands. ..
  21. Zhu Y, Webster S, Flower D, Woll P. Interleukin-8/CXCL8 is a growth factor for human lung cancer cells. Br J Cancer. 2004;91:1970-6 pubmed
    ..In conclusion, IL-8 can act as an autocrine and/or paracrine growth factor for lung cancer cells, and the mitogenic function of IL-8 in lung cancer is mediated mainly by CXCR1 receptor. ..
  22. Wareing M, Shea A, Inglis C, Dias P, Sarawar S. CXCR2 is required for neutrophil recruitment to the lung during influenza virus infection, but is not essential for viral clearance. Viral Immunol. 2007;20:369-78 pubmed
    ..Thus, it appears that CXCR2 is the major receptor mediating neutrophil trafficking to the lung during influenza virus infection, but that neutrophils do not play an essential role in viral clearance. ..
  23. Govindaraju V, Michoud M, Al Chalabi M, Ferraro P, Powell W, Martin J. Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration. Am J Physiol Cell Physiol. 2006;291:C957-65 pubmed
    ..These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF. ..
  24. Li A, Varney M, Valasek J, Godfrey M, Dave B, Singh R. Autocrine role of interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production and angiogenesis. Angiogenesis. 2005;8:63-71 pubmed
    ..Together these data suggest that IL-8 functions as an important autocrine growth and angiogenic factor in regulating multiple biological activities in endothelial cells. ..
  25. Huang J, Yao J, Zhang L, Bourne P, Quinn A, di Sant agnese P, et al. Differential expression of interleukin-8 and its receptors in the neuroendocrine and non-neuroendocrine compartments of prostate cancer. Am J Pathol. 2005;166:1807-15 pubmed
  26. Keane M, Belperio J, Xue Y, Burdick M, Strieter R. Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer. J Immunol. 2004;172:2853-60 pubmed
    ..The results of these studies support the notion that CXCR2 mediates the angiogenic activity of ELR(+) CXC chemokines in a preclinical model of lung cancer. ..
  27. Strieter R, Keane M, Burdick M, Sakkour A, Murray L, Belperio J. The role of CXCR2/CXCR2 ligands in acute lung injury. Curr Drug Targets Inflamm Allergy. 2005;4:299-303 pubmed
    ..The importance of the biology of CXC chemokines in ALI/ARDS will be discussed in this review. ..
  28. Omari K, John G, Lango R, Raine C. Role for CXCR2 and CXCL1 on glia in multiple sclerosis. Glia. 2006;53:24-31 pubmed
  29. Horikawa T, Kaizaki Y, Kato H, Furukawa M, Yoshizaki T. Expression of interleukin-8 receptor A predicts poor outcome in patients with nasopharyngeal carcinoma. Laryngoscope. 2005;115:62-7 pubmed
    ..2%, that in IL8RA-positive patients was only 33.3%. The study results suggest that the expression of IL8RA in tumor cells becomes an important indicator of poor prognosis in nasopharyngeal carcinoma. ..
  30. Yang H, Woodson K, Taylor P, Pietinen P, Albanes D, Virtamo J, et al. Genetic variation in interleukin 8 and its receptor genes and its influence on the risk and prognosis of prostate cancer among Finnish men in a large cancer prevention trial. Eur J Cancer Prev. 2006;15:249-53 pubmed
    ..Although none of the SNPs studied are likely to have major effects on prostate cancer susceptibility, a role for other polymorphisms associated within these genes cannot be excluded. ..
  31. Russo R, Guabiraba R, Garcia C, Barcelos L, Roffe E, Souza A, et al. Role of the chemokine receptor CXCR2 in bleomycin-induced pulmonary inflammation and fibrosis. Am J Respir Cell Mol Biol. 2009;40:410-21 pubmed publisher
    ..An effect on neutrophils does not appear to account for the major effects of the blockade of CXCR2 in the system. ..
  32. Dal Secco D, Cunha T, Freitas A, Alves Filho J, Souto F, Fukada S, et al. Hydrogen sulfide augments neutrophil migration through enhancement of adhesion molecule expression and prevention of CXCR2 internalization: role of ATP-sensitive potassium channels. J Immunol. 2008;181:4287-98 pubmed
    ..Together, our data suggest that during the inflammatory response, H(2)S augments neutrophil adhesion and locomotion, by a mechanism dependent on K(ATP)(+) channels. ..
  33. Kamali Sarvestani E, Aliparasti M, Atefi S. Association of interleukin-8 (IL-8 or CXCL8) -251T/A and CXCR2 +1208C/T gene polymorphisms with breast cancer. Neoplasma. 2007;54:484-9 pubmed
    ..6% and 7.1%, respectively; p=0.07). In conclusion, IL-8 -251T/A polymorphism is associated with development of invasive ductal carcinoma type of breast cancer while CXCR2 +1208C/T polymorphism may affect the disease progression. ..
  34. Boisvert W, Rose D, Johnson K, Fuentes M, Lira S, Curtiss L, et al. Up-regulated expression of the CXCR2 ligand KC/GRO-alpha in atherosclerotic lesions plays a central role in macrophage accumulation and lesion progression. Am J Pathol. 2006;168:1385-95 pubmed
  35. Singh S, Varney M, Singh R. Host CXCR2-dependent regulation of melanoma growth, angiogenesis, and experimental lung metastasis. Cancer Res. 2009;69:411-5 pubmed publisher
    ..Together, these studies show the importance of host CXCR2-dependent CXCL-8-mediated angiogenesis in the regulation of melanoma growth and metastasis. ..
  36. Chapman R, Phillips J, Hipkin R, Curran A, Lundell D, Fine J. CXCR2 antagonists for the treatment of pulmonary disease. Pharmacol Ther. 2009;121:55-68 pubmed publisher
    ..Clinical trials evaluating small molecule CXCR2 antagonists in COPD, asthma and cystic fibrosis are currently underway. These studies hold considerable promise for identifying novel and efficacious treatments of pulmonary disorders. ..
  37. Reutershan J, Morris M, Burcin T, Smith D, Chang D, Saprito M, et al. Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung. J Clin Invest. 2006;116:695-702 pubmed
    ..Our data revealed what we believe to be a previously unrecognized role of endothelial and epithelial CXCR2 in LPS-induced PMN recruitment and lung injury. ..
  38. Wente M, Keane M, Burdick M, Friess H, Buchler M, Ceyhan G, et al. Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis. Cancer Lett. 2006;241:221-7 pubmed
  39. Savage S, Abnet C, Mark S, Qiao Y, Dong Z, Dawsey S, et al. Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2004;13:2251-7 pubmed
    ..These variants could confer an altered IL8 expression pattern or interact with environmental factors to increase the risk for inflammation and GCC. ..
  40. Buanne P, Di Carlo E, Caputi L, Brandolini L, Mosca M, Cattani F, et al. Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice. J Leukoc Biol. 2007;82:1239-46 pubmed
    ..Our data demonstrate that CXCR2 plays a key pathophysiological role in experimental UC, suggesting that CXCR2 activation may represent a relevant pharmacological target for the design of novel pharmacological treatments in human UC. ..
  41. Carlson T, Kroenke M, Rao P, Lane T, Segal B. The Th17-ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease. J Exp Med. 2008;205:811-23 pubmed publisher
  42. Qiu Y, Zhu J, Bandi V, Atmar R, Hattotuwa K, Guntupalli K, et al. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;168:968-75 pubmed
    ..Thus, in COPD, in addition to CXCL8 and CXCR1, CXCL5 and CXCR2 appear to play important roles in the airway neutrophilia characteristic of severe exacerbations. ..
  43. Wilson C, Purcell C, Seaton A, Oladipo O, Maxwell P, O Sullivan J, et al. Chemotherapy-induced CXC-chemokine/CXC-chemokine receptor signaling in metastatic prostate cancer cells confers resistance to oxaliplatin through potentiation of nuclear factor-kappaB transcription and evasion of apoptosis. J Pharmacol Exp Ther. 2008;327:746-59 pubmed publisher
    ..Our results further support NF-kappaB activity as an important determinant of cancer cell sensitivity to oxaliplatin and identify the induction of autocrine CXCR2 signaling as a novel mode of resistance to this drug. ..
  44. Pease J, Sabroe I. The role of interleukin-8 and its receptors in inflammatory lung disease: implications for therapy. Am J Respir Med. 2002;1:19-25 pubmed
    ..Clinical trials of such compounds will ultimately provide crucial information currently lacking and will define whether or not IL-8 blockade provides future therapy in pulmonary disease. ..
  45. Rajarathnam K, Prado G, Fernando H, Clark Lewis I, Navarro J. Probing receptor binding activity of interleukin-8 dimer using a disulfide trap. Biochemistry. 2006;45:7882-8 pubmed
    ..These results demonstrate that only the monomer is a high-affinity ligand for both receptors, and also provide a structural basis for the lower binding affinity of the dimer. ..
  46. Podolin P, Bolognese B, Foley J, Schmidt D, Buckley P, Widdowson K, et al. A potent and selective nonpeptide antagonist of CXCR2 inhibits acute and chronic models of arthritis in the rabbit. J Immunol. 2002;169:6435-44 pubmed
    ..75 nM), suggesting that inhibition of leukocyte migration into the knee joint is a likely mechanism by which the CXCR2 antagonist modulates disease. ..
  47. Kielian T, Barry B, Hickey W. CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses. J Immunol. 2001;166:4634-43 pubmed
    ..These studies demonstrate the importance of the CXCR2 ligands MIP-2 and KC and neutrophils in the acute host response to S. aureus in the brain. ..
  48. Ragozzino D. CXC chemokine receptors in the central nervous system: Role in cerebellar neuromodulation and development. J Neurovirol. 2002;8:559-72 pubmed
  49. Heidemann J, Ogawa H, Dwinell M, Rafiee P, Maaser C, Gockel H, et al. Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2. J Biol Chem. 2003;278:8508-15 pubmed
    ..Supported by the notion that malignant colonic epithelial cells overexpress IL-8, CXCR2 blockade may be a novel target for anti-angiogenic therapy in colorectal adenocarcinoma. ..
  50. Tsai H, Frost E, To V, Robinson S, Ffrench Constant C, Geertman R, et al. The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell. 2002;110:373-83 pubmed
    ..These data suggest that population of presumptive white matter by oligodendrocyte precursors is dependent on localized expression of CXCL1. ..
  51. Fischer F, Santambrogio L, Luo Y, Berman M, Hancock W, Dorf M. Modulation of experimental autoimmune encephalomyelitis: effect of altered peptide ligand on chemokine and chemokine receptor expression. J Neuroimmunol. 2000;110:195-208 pubmed
    ..This report concludes that chemokines and chemokine receptors can be useful tools to follow modulation of autoimmune disease. ..
  52. Olszyna D, Florquin S, Sewnath M, Branger J, Speelman P, van Deventer S, et al. CXC chemokine receptor 2 contributes to host defense in murine urinary tract infection. J Infect Dis. 2001;184:301-7 pubmed
    ..CXC chemokines play an important role in the development of a local inflammatory response to UTI. ..
  53. Li A, Varney M, Singh R. Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials. Clin Cancer Res. 2001;7:3298-304 pubmed