Genomes and Genes
Summary: A 10.8-kDa member of the S-100 family of calcium-binding proteins that can form homo- or heterocomplexes with CALGRANULIN B and a variety of other proteins. The calgranulin A/B heterodimer is known as LEUKOCYTE L1 ANTIGEN COMPLEX. Calgranulin A is found in many cell types including GRANULOCYTES; KERATINOCYTES; and myelomonocytes, and has been shown to act as a chemotactic substance for NEUTROPHILS. Because it is present in acute inflammation but absent in chronic inflammation, it is a useful biological marker for a number of pathological conditions.
- Goto Y, Sanjoba C, Arakaki N, Okamoto M, Saeki K, Onodera T, et al. Accumulation of macrophages expressing MRP8 and MRP14 in skin lesions during Leishmania major infection in BALB/c and RAG-2 knockout mice. Parasitol Int. 2007;56:231-4 pubmed..These data suggest that the accumulation of inflammatory subtype of macrophages in BALB/c mice during L. major infection can be induced without acquired immune responses. ..
- Lee Y, Sohn K, Jang S, Lee Y, Hwang C, Kim K, et al. Anti-apoptotic role of S100A8 in X-ray irradiated keratinocytes. J Dermatol Sci. 2008;51:11-8 pubmed publisher..Furthermore, overexpression of S100A8 significantly protected the X-ray-induced apoptosis. These results suggest that S100A8 have an anti-apoptotic role in X-ray irradiated keratinocytes. ..
- Rosenberger S, Thorey I, Werner S, Boukamp P. A novel regulator of telomerase. S100A8 mediates differentiation-dependent and calcium-induced inhibition of telomerase activity in the human epidermal keratinocyte line HaCaT. J Biol Chem. 2007;282:6126-35 pubmed..We hypothesize that calcium binds to S100A8/S100A9 complexes and alters their composition, thus enabling S100A8 to interact with the telomerase complex and inhibit its activity. ..
- Suryono -, Kido J, Hayashi N, Kataoka M, Shinohara Y, Nagata T. Norepinephrine stimulates calprotectin expression in human monocytic cells. J Periodontal Res. 2006;41:159-64 pubmed..Norepinephrine, a stress modulator, stimulated calprotectin expression in human monocytic cells. Calprotectin expression may be regulated by stress in addition to inflammatory factors. ..
- Hsu K, Passey R, Endoh Y, Rahimi F, Youssef P, Yen T, et al. Regulation of S100A8 by glucocorticoids. J Immunol. 2005;174:2318-26 pubmed..Results support the proposal that A8 has anti-inflammatory properties that may be independent of hetero-complex formation with A9 and may also enable localized defense in the absence of overriding deleterious host responses. ..
- Schenten V, Melchior C, Steinckwich N, Tschirhart E, Bréchard S. Sphingosine kinases regulate NOX2 activity via p38 MAPK-dependent translocation of S100A8/A9. J Leukoc Biol. 2011;89:587-96 pubmed publisher..In addition, p38 MAPK was found to be regulated by SphKs. These results define a pathway leading to NOX2 activation, in which p38 MAPK-mediated S100A8/A9 translocation is regulated by Ca(2+) store depletion-dependent SphK activation. ..
- Baillet A, Trocme C, Berthier S, Arlotto M, Grange L, Chenau J, et al. Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases. Rheumatology (Oxford). 2010;49:671-82 pubmed publisher..We investigated SF and serum proteomic fingerprints of patients suffering from RA, OA and other miscellaneous inflammatory arthritides (MIAs) in order to identify RA-specific biomarkers...
- Sorenson B, Khammanivong A, Guenther B, Ross K, Herzberg M. IL-1 receptor regulates S100A8/A9-dependent keratinocyte resistance to bacterial invasion. Mucosal Immunol. 2012;5:66-75 pubmed publisher..These data strongly suggest that infected epithelial cells release IL-1? to signal neighboring keratinocytes in a paracrine manner, promoting S100A8/A9-dependent resistance to invasive L. monocytogenes. ..
- Ito Y, Arai K, Nozawa R, Yoshida H, Hirokawa M, Fukushima M, et al. S100A8 and S100A9 expression is a crucial factor for dedifferentiation in thyroid carcinoma. Anticancer Res. 2009;29:4157-61 pubmed..S100A8 plays an important role in dedifferentiation of thyroid carcinoma possibly by forming a complex with S100A9. ..
- Ghavami S, Chitayat S, Hashemi M, Eshraghi M, Chazin W, Halayko A, et al. S100A8/A9: a Janus-faced molecule in cancer therapy and tumorgenesis. Eur J Pharmacol. 2009;625:73-83 pubmed publisher..Clearly, there is a dichotomy and future investigations into the role of S100A8/A9 in cancer biology need to consider both sides of the same coin. ..
- Grimbaldeston M, Geczy C, Tedla N, Finlay Jones J, Hart P. S100A8 induction in keratinocytes by ultraviolet A irradiation is dependent on reactive oxygen intermediates. J Invest Dermatol. 2003;121:1168-74 pubmed..These results suggest that UVA-induced S100A8 is expressed by keratinocytes in response to generation of reactive oxygen intermediates. ..
- Ehrchen J, Sunderkotter C, Foell D, Vogl T, Roth J. The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J Leukoc Biol. 2009;86:557-66 pubmed publisher..Thus, S100A8/S100A9 plays a pivotal role during amplification of inflammation and represents a promising new therapeutic target. ..
- Tolson J, Flad T, Gnau V, Dihazi H, Hennenlotter J, Beck A, et al. Differential detection of S100A8 in transitional cell carcinoma of the bladder by pair wise tissue proteomic and immunohistochemical analysis. Proteomics. 2006;6:697-708 pubmed..We report the inflammation-associated calcium binding protein S100A8 (MRP-8, calgranulin A) to be highly expressed in tumor cells in contrast to normal urothelium in 50% of the samples, as well as two ..
- Pouliot P, Plante I, Raquil M, Tessier P, Olivier M. Myeloid-related proteins rapidly modulate macrophage nitric oxide production during innate immune response. J Immunol. 2008;181:3595-601 pubmed..Finally, we observed this effect to be dependent on TLR4. Collectively, our study unravels the importance of MRPs as potent new inducers of Mphi NO production. ..
- Hirono K, Foell D, Xing Y, Miyagawa Tomita S, Ye F, Ahlmann M, et al. Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki disease. J Am Coll Cardiol. 2006;48:1257-64 pubmed
- Voss A, Bode G, Sopalla C, Benedyk M, Varga G, Bohm M, et al. Expression of S100A8/A9 in HaCaT keratinocytes alters the rate of cell proliferation and differentiation. FEBS Lett. 2011;585:440-6 pubmed publisher..S100A8/A9 is induced in epithelial cells in response to stress. Therefore, S100A8/A9-mediated growth arrest could have implications for tissue remodeling and repair. ..
- Ichikawa M, Williams R, Wang L, Vogl T, Srikrishna G. S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res. 2011;9:133-48 pubmed publisher..Our results thus reveal a novel role for myeloid-derived S100A8/A9 in activating specific downstream genes associated with tumorigenesis and in promoting tumor growth and metastasis. ..
- Ryckman C, Vandal K, Rouleau P, Talbot M, Tessier P. Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. J Immunol. 2003;170:3233-42 pubmed..These studies 1) show that S100A8, S100A9, and S100A8/A9 are potent stimulators of neutrophils and 2) strongly suggest that these proteins are involved in neutrophil migration to inflammatory sites. ..
- Vandal K, Rouleau P, Boivin A, Ryckman C, Talbot M, Tessier P. Blockade of S100A8 and S100A9 suppresses neutrophil migration in response to lipopolysaccharide. J Immunol. 2003;171:2602-9 pubmed..These results suggest that S100A8 and S100A9 play a role in the inflammatory response to LPS by inducing the release of neutrophils from the bone marrow and directing their migration to the inflammatory site. ..
- Bouzidi F, Doussiere J. Binding of arachidonic acid to myeloid-related proteins (S100A8/A9) enhances phagocytic NADPH oxidase activation. Biochem Biophys Res Commun. 2004;325:1060-5 pubmed..AA-loaded S100A8/A9 increases oxidase activation probably by decreasing the deactivation rate. ..
- Nacken W, Kerkhoff C. The hetero-oligomeric complex of the S100A8/S100A9 protein is extremely protease resistant. FEBS Lett. 2007;581:5127-30 pubmed
- Halayko A, Ghavami S. S100A8/A9: a mediator of severe asthma pathogenesis and morbidity?. Can J Physiol Pharmacol. 2009;87:743-55 pubmed publisher..This review highlights some key issues related to this hypothesis and provides a template for future research. ..
- Arai K, Takano S, Teratani T, Ito Y, Yamada T, Nozawa R. S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast. Curr Cancer Drug Targets. 2008;8:243-52 pubmed
- Ghavami S, Rashedi I, Dattilo B, Eshraghi M, Chazin W, Hashemi M, et al. S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway. J Leukoc Biol. 2008;83:1484-92 pubmed publisher..RAGE small interfering RNA pretreatment abrogated the S100A8/A9-induced NF-kappaB activation. Our data indicate that S100A8/A9-promoted cell growth occurs through RAGE signaling and activation of NF-kappaB. ..
- Sohnle P, Hunter M, Hahn B, Chazin W. Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor-related proteins 8 and 14). J Infect Dis. 2000;182:1272-5 pubmed..These results suggest that intact calprotectin, consisting of a heterodimer of MRP8 and MRP14, is necessary to form a zinc-binding site capable of inhibiting microbial growth. ..
- Hermani A, Hess J, De Servi B, Medunjanin S, Grobholz R, Trojan L, et al. Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer. Clin Cancer Res. 2005;11:5146-52 pubmed..Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH. ..
- Viemann D, Strey A, Janning A, Jurk K, Klimmek K, Vogl T, et al. Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells. Blood. 2005;105:2955-62 pubmed..MRP8/MRP14 may represent novel targets for anti-inflammatory strategies. ..
- Roth J, Vogl T, Sorg C, Sunderkotter C. Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol. 2003;24:155-8 pubmed..S100A12 directly activates endothelial cells, mononuclear phagocytes and lymphocytes through interaction with the receptor for advanced glycation end products. Thus, these S100-proteins are attractive targets to modulate inflammation. ..
- Thorey I, Roth J, Regenbogen J, Halle J, Bittner M, Vogl T, et al. The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes. J Biol Chem. 2001;276:35818-25 pubmed
- Sickert D, Aust D, Langer S, Baretton G, Dieter P. Characterization of macrophage subpopulations and microvessel density in carcinomas of the gastrointestinal tract. Anticancer Res. 2007;27:1693-700 pubmed..The observed common characteristics regarding macrophage attraction, lymphocyte suppression and microvessel density suggested that these mechanisms are regulated similarly in all carcinomas of the GI-tract. ..
- Yong H, Moon A. Roles of calcium-binding proteins, S100A8 and S100A9, in invasive phenotype of human gastric cancer cells. Arch Pharm Res. 2007;30:75-81 pubmed..Taken together, this study revealed a functional contribution of S100A8 and S100A9 proteins to processes required for malignant progression including invasion, migration and proteinase expression in SNU484 human gastric cancer cells. ..
- Sinha P, Okoro C, Foell D, Freeze H, Ostrand Rosenberg S, Srikrishna G. Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol. 2008;181:4666-75 pubmed..Since S100A8/A9 activation of MDSC is through the NF-kappaB signaling pathway, drugs that target this pathway may reduce MDSC levels and be useful therapeutic agents in conjunction with active immunotherapy in cancer patients. ..
- Jung D, Park J, Lee E, Lee H, Joh J, Kwon C, et al. Combined use of myeloid-related protein 8/14 and procalcitonin as diagnostic markers for acute allograft rejection in kidney transplantation recipients. Transpl Immunol. 2008;18:338-43 pubmed..These results indicate that the combined use of MRP 8/14 and PCT serum concentrations can allow one to distinguish between allograft rejection and other inflammatory processes, such as infection. ..
- Hessian P, Fisher L. The heterodimeric complex of MRP-8 (S100A8) and MRP-14 (S100A9). Antibody recognition, epitope definition and the implications for structure. Eur J Biochem. 2001;268:353-63 pubmed
- van Lent P, Grevers L, Schelbergen R, Blom A, Geurts J, Sloetjes A, et al. S100A8 causes a shift toward expression of activatory Fc? receptors on macrophages via toll-like receptor 4 and regulates Fc? receptor expression in synovium during chronic experimental arthritis. Arthritis Rheum. 2010;62:3353-64 pubmed publisher..This study was undertaken to study the active involvement of S100A8, S100A9, and S100A8/S100A9 in Fc?R regulation in murine macrophages and synovium during AIA...
- Ang C, Nedjadi T, Sheikh A, Tweedle E, Tonack S, Honap S, et al. Smad4 loss is associated with fewer S100A8-positive monocytes in colorectal tumors and attenuated response to S100A8 in colorectal and pancreatic cancer cells. Carcinogenesis. 2010;31:1541-51 pubmed publisher..In conclusion, Smad4 loss alters the tumor's interaction with stromal myeloid cells and the tumor cells' response to the stromal chemokine, S100A8. ..
- Schenten V, Bréchard S, Plançon S, Melchior C, Frippiat J, Tschirhart E. iPLA2, a novel determinant in Ca2+- and phosphorylation-dependent S100A8/A9 regulated NOX2 activity. Biochim Biophys Acta. 2010;1803:840-7 pubmed publisher..In conclusion, we have characterized a pathway leading to NOX2 activation in which iPLA(2)-regulated p38 MAPK activity is a key regulator of S100A8/A9 translocation via S100A9 phosphorylation. ..
- Berthier S, Paclet M, Lerouge S, Roux F, Vergnaud S, Coleman A, et al. Changing the conformation state of cytochrome b558 initiates NADPH oxidase activation: MRP8/MRP14 regulation. J Biol Chem. 2003;278:25499-508 pubmed..Moreover, MRP8/MRP14 dimer behaves as a positive mediator of phagocyte NADPH oxidase regulation. ..
- Ahmad A, Bayley D, He S, Stockley R. Myeloid related protein-8/14 stimulates interleukin-8 production in airway epithelial cells. Am J Respir Cell Mol Biol. 2003;29:523-30 pubmed
- Frosch M, Vogl T, Waldherr R, Sorg C, Sunderkotter C, Roth J. Expression of MRP8 and MRP14 by macrophages is a marker for severe forms of glomerulonephritis. J Leukoc Biol. 2004;75:198-206 pubmed..In addition, our findings reflect differences in the inflammatory mechanisms underlying the various forms of GN, as they revealed that distinct macrophage subpopulations prevail in the different forms of GN. ..
- Nicolas E, Ramus C, Berthier S, Arlotto M, Bouamrani A, Lefebvre C, et al. Expression of S100A8 in leukemic cells predicts poor survival in de novo AML patients. Leukemia. 2011;25:57-65 pubmed publisher..The 10,800-Da marker was identified by MS peptide sequencing as S100A8 (also designated MRP8 or calgranulin A)...
- Srikrishna G. S100A8 and S100A9: new insights into their roles in malignancy. J Innate Immun. 2012;4:31-40 pubmed publisher..Elucidating molecular pathways mediated by these proteins promises to provide potential novel targets for the development of cancer therapeutics and to establish valid biomarkers to identify early stages of tumor progression. ..
- Dhiman R, Venkatasubramanian S, Paidipally P, Barnes P, Tvinnereim A, Vankayalapati R. Interleukin 22 inhibits intracellular growth of Mycobacterium tuberculosis by enhancing calgranulin A expression. J Infect Dis. 2014;209:578-87 pubmed publisher..indicated that recombinant IL-22 (rIL-22) enhances the expression of an intracellular signaling molecule, calgranulin A. This was confirmed by real-time polymerase chain reaction, Western blot, and confocal microscopy...
- Lim S, Raftery M, Goyette J, Hsu K, Geczy C. Oxidative modifications of S100 proteins: functional regulation by redox. J Leukoc Biol. 2009;86:577-87 pubmed publisher..This review offers an explanation for the disparate, functional roles of S100A8 and S100A9 based on emerging data that post-translational, oxidative modifications may act as a regulatory switch. ..
- Goto Y, Sanjoba C, Asada M, Saeki K, Onodera T, Matsumoto Y. Adhesion of MRP8/14 to amastigotes in skin lesions of Leishmania major-infected mice. Exp Parasitol. 2008;119:80-6 pubmed publisher..MRP14 adhered to not only amastigotes, but also promastigotes, suggesting receptor molecules for MRP14 are expressed commonly in both developmental stages. ..
- Greenlee K, Corry D, Engler D, Matsunami R, Tessier P, Cook R, et al. Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation. J Immunol. 2006;177:7312-21 pubmed..These findings provide a molecular mechanism to explain the enhanced clearance of lung inflammatory cells through the airway and reveal a novel approach to target new therapies for asthma. ..
- Kane D, Roth J, Frosch M, Vogl T, Bresnihan B, Fitzgerald O. Increased perivascular synovial membrane expression of myeloid-related proteins in psoriatic arthritis. Arthritis Rheum. 2003;48:1676-85 pubmed..Moreover, MRP expression is reduced following MTX treatment. MRP proteins may represent a novel therapeutic target in inflammatory arthritis. ..
- Broome A, Ryan D, Eckert R. S100 protein subcellular localization during epidermal differentiation and psoriasis. J Histochem Cytochem. 2003;51:675-85 pubmed..These studies also indicate, as reported previously, that S100A7, S100A8, and S100A9 expression is markedly altered in psoriasis, suggesting a role for these proteins in disease pathogenesis. ..
- Wulffraat N, Haas P, Frosch M, De Kleer I, Vogl T, Brinkman D, et al. Myeloid related protein 8 and 14 secretion reflects phagocyte activation and correlates with disease activity in juvenile idiopathic arthritis treated with autologous stem cell transplantation. Ann Rheum Dis. 2003;62:236-41 pubmed..This indicates a role of macrophage activation in the pathogenesis of JIA. The occurrence of MAS in three patients in this study was not preceded by significant changes in MRP8/MRP14 concentration. ..
- Xu K, Yen T, Geczy C. Il-10 up-regulates macrophage expression of the S100 protein S100A8. J Immunol. 2001;166:6358-66 pubmed..A8 exhibits pleiotropic effects, and the high levels secreted as a result of IL-10 synergy may regulate untoward inflammatory damage by virtue of its an antioxidant capacity. ..
- Eue I, Pietz B, Storck J, Klempt M, Sorg C. Transendothelial migration of 27E10+ human monocytes. Int Immunol. 2000;12:1593-604 pubmed..Thus, MRP8/14 substantially contributes to the recruitment of monocytes to an inflammatory site. ..