Genomes and Genes
Summary: A 13.2-kDa member of the S-100 family of calcium-binding proteins that can form homo- or heterocomplexes with CALGRANULIN A and a variety of other proteins. The calgranulin A/B heterodimer is known as LEUKOCYTE L1 ANTIGEN COMPLEX. Calgranulin B is expressed at high concentrations in GRANULOCYTES during early monocyte differentiation, and serum calgranulin B levels are elevated in many inflammatory disorders such as CYSTIC FIBROSIS.
- Shimizu K, Libby P, Rocha V, Folco E, Shubiki R, Grabie N, et al. Loss of myeloid related protein-8/14 exacerbates cardiac allograft rejection. Circulation. 2011;124:2920-32 pubmed publisher..The absence of MRP-14 markedly increased T-cell activation and exacerbated allograft rejection, indicating a previously unrecognized role for MRP-14 in immune cell biology. ..
- Pagano R, Sampaio S, Juliano L, Juliano M, Giorgi R. The C-terminus of murine S100A9 inhibits spreading and phagocytic activity of adherent peritoneal cells. Inflamm Res. 2005;54:204-10 pubmed..These results suggest a modulator effect of the C-terminus of S100A9 protein on the function of adherent peritoneal cells. ..
- Bhattacharjee R, Kim J, Alotaibi W, Kheirandish Gozal L, Capdevila O, Gozal D. Endothelial dysfunction in children without hypertension: potential contributions of obesity and obstructive sleep apnea. Chest. 2012;141:682-691 pubmed publisher..Although the mechanisms underlying endothelial dysfunction remain unclear, a potential role for MRP8/14 as an inflammatory biomarker of endothelial dysfunction is suggested. ..
- Yoo B, Shin Y, Lim S, Hong S, Jeong S, Park J. Evaluation of calgranulin B in stools from the patients with colorectal cancer. Dis Colon Rectum. 2008;51:1703-9 pubmed publisher..We assessed the clinical usefulness of calgranulin B as a stool marker for colorectal cancer in a pilot study of patients with colorectal cancer...
- Chen Y, Yan W, Geczy C, Brown M, Thomas R. Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis. Arthritis Res Ther. 2009;11:R39 pubmed publisher..These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients. ..
- Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen M, et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med. 2007;13:1042-9 pubmed..Therefore Mrp8-Mrp14 complexes are new inflammatory components that amplify phagocyte activation during sepsis upstream of TNFalpha-dependent effects. ..
- Lood C, Stenstrom M, Tydén H, Gullstrand B, Källberg E, Leanderson T, et al. Protein synthesis of the pro-inflammatory S100A8/A9 complex in plasmacytoid dendritic cells and cell surface S100A8/A9 on leukocyte subpopulations in systemic lupus erythematosus. Arthritis Res Ther. 2011;13:R60 pubmed publisher..Importantly, pDCs were able to synthesize S100A8/A9 proteins and up-regulate the cell surface expression upon immune complex-stimulation. Thus, S100A8/A9 may be a potent target for treatment of inflammatory diseases such as SLE. ..
- Sheikh A, Vimalachandran D, Thompson C, Jenkins R, Nedjadi T, Shekouh A, et al. The expression of S100A8 in pancreatic cancer-associated monocytes is associated with the Smad4 status of pancreatic cancer cells. Proteomics. 2007;7:1929-40 pubmed..In conclusion, our study provides an extensive analysis of S100A8 and S100A9 in pancreatic disease and highlights a potentially important relationship between pancreatic cancer cells and their surrounding microenvironment. ..
- Moon A, Yong H, Song J, Cukovic D, Salagrama S, Kaplan D, et al. Global gene expression profiling unveils S100A8/A9 as candidate markers in H-ras-mediated human breast epithelial cell invasion. Mol Cancer Res. 2008;6:1544-53 pubmed publisher..Our gene profile data provide useful information which may lead to the identification of additional potential targets for the prognosis and/or therapy of metastatic breast cancer. ..
- Gebhardt C, Nemeth J, Angel P, Hess J. S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol. 2006;72:1622-31 pubmed..Altogether, its expression and potential cytokine-like function in inflammation and in cancer suggests that S100A8/A9 may play a key role in inflammation-associated cancer. ..
- Anceriz N, Vandal K, Tessier P. S100A9 mediates neutrophil adhesion to fibronectin through activation of beta2 integrins. Biochem Biophys Res Commun. 2007;354:84-9 pubmed..In contrast, neutrophil adhesion to fibronectin was completely inhibited by anti-beta2 integrins, suggesting that S100A9-induced specific activation of beta2 integrin is essential to neutrophil adhesion. ..
- Kawai H, Minamiya Y, Takahashi N. Prognostic impact of S100A9 overexpression in non-small cell lung cancer. Tumour Biol. 2011;32:641-6 pubmed publisher..1-0.8; P=0.02). Our results suggest that overexpression of S100A9 is associated with a poor prognosis among NSCLC patients and could serve as a marker identifying patients who are at high risk, even at an early pathological stage. ..
- Ehlermann P, Eggers K, Bierhaus A, Most P, Weichenhan D, Greten J, et al. Increased proinflammatory endothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc Diabetol. 2006;5:6 pubmed..Thus, blocking heterodimeric S100A8/S100A9 might represent a novel therapeutic modality in treating atherosclerosis. ..
- Holzinger D, Frosch M, Kastrup A, Prince F, Otten M, van Suijlekom Smit L, et al. The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis. Ann Rheum Dis. 2012;71:974-80 pubmed publisher..Analysis of myeloid-related protein 8 and 14 complex (MRP8/14) serum concentrations is a potential new tool to support the diagnosis of systemic-onset juvenile idiopathic arthritis (SJIA) in the presence of fever of unknown origin...
- Leukert N, Sorg C, Roth J. Molecular basis of the complex formation between the two calcium-binding proteins S100A8 (MRP8) and S100A9 (MRP14). Biol Chem. 2005;386:429-34 pubmed..Furthermore, amino acids Y16 and F68 prevent homodimerization of human S100A8. These data demonstrate for the first time the functional relevance of distinct hydrophobic amino acids for human S100A8/S100A9 complex formation in vivo. ..
- Stocca A, O Toole D, Hynes N, Hynes S, Mashayekhi K, McGinley L, et al. A role for MRP8 in in stent restenosis in diabetes. Atherosclerosis. 2012;221:325-32 pubmed publisher..Thus, MRP8/14 likely plays a role in exaggerated ISR in diabetes mellitus, and MRP8 inhibition may be useful in improving outcome after stent placement in diabetes mellitus. ..
- Loser K, Vogl T, Voskort M, Lueken A, Kupas V, Nacken W, et al. The Toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8+ T cells. Nat Med. 2010;16:713-7 pubmed publisher..These results demonstrate a link between local expression of DAMP molecules and the development of systemic autoimmunity. ..
- Paclet M, Berthier S, Kuhn L, Garin J, Morel F. Regulation of phagocyte NADPH oxidase activity: identification of two cytochrome b558 activation states. FASEB J. 2007;21:1244-55 pubmed..MRPs induce the switch between the partially and the fully "open" cytochrome b558 conformation. Moreover, their effect was independent of p67-phox. Data point out two potential cytochrome b558 activation states...
- Ha T, Chang K, Kim J, Kim H, Kim S, Chong Y, et al. S100a9 knockdown decreases the memory impairment and the neuropathology in Tg2576 mice, AD animal model. PLoS ONE. 2010;5:e8840 pubmed publisher..Thus, the inhibition of S100a9 is a possible target for AD therapy. ..
- de Seny D, Fillet M, Ribbens C, Maree R, Meuwis M, Lutteri L, et al. Monomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis. Clin Chem. 2008;54:1066-75 pubmed publisher..SELDI-TOF MS analyses identified several calgranulin proteins [S100A8 (calgranulin A), S100A9 (calgranulin B), S100A9*, and S100A12 (calgranulin C)], serum amyloid A (SAA), SAA des-Arg (SAA-R), and SAA des-Arg/des-Ser (..
- Goncalves A, Charafe Jauffret E, Bertucci F, Audebert S, Toiron Y, Esterni B, et al. Protein profiling of human breast tumor cells identifies novel biomarkers associated with molecular subtypes. Mol Cell Proteomics. 2008;7:1420-33 pubmed publisher..Our study shows the potential of integrated genomics and proteomics profiling to improve molecular knowledge of complex tumor phenotypes and identify biomarkers with valuable diagnostic or prognostic values. ..
- Grote J, König S, Ackermann D, Sopalla C, Benedyk M, Los M, et al. Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional regulators of S100A9 gene expression. BMC Mol Biol. 2006;7:48 pubmed..The latter may indicate a possible link between S100 and inflammation-associated cancer. ..
- Hiratsuka S, Watanabe A, Aburatani H, Maru Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol. 2006;8:1369-75 pubmed..Thus, the S100A8 and S100A9 pathway may be common to both myeloid cell recruitment and tumour-cell invasion. ..
- Sunahori K, Yamamura M, Yamana J, Takasugi K, Kawashima M, Yamamoto H, et al. The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis. Arthritis Res Ther. 2006;8:R69 pubmed..These results indicate that the S100A8/A9 heterodimer, secreted extracellularly from activated tissue macrophages, may amplify proinflammatory cytokine responses through activation of NF-kappaB and p38 MAPK pathways in RA. ..
- Shepherd C, Goyette J, Utter V, Rahimi F, Yang Z, Geczy C, et al. Inflammatory S100A9 and S100A12 proteins in Alzheimer's disease. Neurobiol Aging. 2006;27:1554-63 pubmed..This study indicates a potential role for pro-inflammatory S100A9 and S100A12 in pathogenesis caused by inflammation and protein complex formation in AD. ..
- Rahimi F, Hsu K, Endoh Y, Geczy C. FGF-2, IL-1beta and TGF-beta regulate fibroblast expression of S100A8. FEBS J. 2005;272:2811-27 pubmed..Up-regulation of S100A8 by FGF-2/IL-1beta, down-regulation by TGF-beta, and its time-dependent expression in wound fibroblasts suggest a role in fibroblast differentiation at sites of inflammation and repair. ..
- Inaba H, Hokamura K, Nakano K, Nomura R, Katayama K, Nakajima A, et al. Upregulation of S100 calcium-binding protein A9 is required for induction of smooth muscle cell proliferation by a periodontal pathogen. FEBS Lett. 2009;583:128-34 pubmed publisher..gingivalis on transformation and proliferation of hAOSMCs. Our data suggested that upregulation of S100A9 mediated by P. gingivalis is an important event in the development of aortic intimal hyperplasia. ..
- Hibino T, Sakaguchi M, Miyamoto S, Yamamoto M, Motoyama A, Hosoi J, et al. S100A9 is a novel ligand of EMMPRIN that promotes melanoma metastasis. Cancer Res. 2013;73:172-83 pubmed publisher..Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions. ..
- Erez O, Romero R, Tarca A, Chaiworapongsa T, Kim Y, Than N, et al. Differential expression pattern of genes encoding for anti-microbial peptides in the fetal membranes of patients with spontaneous preterm labor and intact membranes and those with preterm prelabor rupture of the membranes. J Matern Fetal Neonatal Med. 2009;22:1103-15 pubmed publisher..The mRNA expression of alpha-defensin-1, beta-defensin-1, calgranulin B and granulysin in the fetal membranes was determined by qRT-PCR...
- Martinsson H, Yhr M, Enerback C. Expression patterns of S100A7 (psoriasin) and S100A9 (calgranulin-B) in keratinocyte differentiation. Exp Dermatol. 2005;14:161-8 pubmed..These findings support the hypothesis that these two S100 proteins are involved in keratinocyte differentiation. ..
- Kido J, Hayashi N, Kataoka M, Nagata T. Calprotectin expression in human monocytes: induction by porphyromonas gingivalis lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-1beta. J Periodontol. 2005;76:437-42 pubmed..These results demonstrate that P-LPS, TNF-alpha, and IL-1beta induce calprotectin production from human monocytes and that this production is associated with the activation of DNA C/EBPalpha binding complex. ..
- Bouma G, Coppens J, Lam Tse W, Luini W, Sintnicolaas K, Levering W, et al. An increased MRP8/14 expression and adhesion, but a decreased migration towards proinflammatory chemokines of type 1 diabetes monocytes. Clin Exp Immunol. 2005;141:509-17 pubmed
- Kerkhoff C, Nacken W, Benedyk M, Dagher M, Sopalla C, Doussiere J. The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67phox and Rac-2. FASEB J. 2005;19:467-9 pubmed..It is concluded that S100A8/A9 plays an important role in phagocyte NADPH oxidase activation. ..
- Henke M, Renner A, Rubin B, Gyves J, Lorenz E, Koo J. Up-regulation of S100A8 and S100A9 protein in bronchial epithelial cells by lipopolysaccharide. Exp Lung Res. 2006;32:331-47 pubmed..This finding suggests that S100A8 and S100A9 are involved in the innate defense of the bronchial epithelium. ..
- Hermani A, De Servi B, Medunjanin S, Tessier P, Mayer D. S100A8 and S100A9 activate MAP kinase and NF-kappaB signaling pathways and trigger translocation of RAGE in human prostate cancer cells. Exp Cell Res. 2006;312:184-97 pubmed..In summary, our findings show that S100A8 and S100A9 are linked to the activation of important features of prostate cancer cells. ..
- Soyfoo M, Roth J, Vogl T, Pochet R, Decaux G. Phagocyte-specific S100A8/A9 protein levels during disease exacerbations and infections in systemic lupus erythematosus. J Rheumatol. 2009;36:2190-4 pubmed publisher..Serum levels of S100A8/A9 are significantly raised in SLE versus pSS patients and healthy controls and can be correlated to a disease activity index. S100A8/A9 is a more relevant marker of infection in SLE patients. ..
- Wittkowski H, Kuemmerle Deschner J, Austermann J, Holzinger D, Goldbach Mansky R, Gramlich K, et al. MRP8 and MRP14, phagocyte-specific danger signals, are sensitive biomarkers of disease activity in cryopyrin-associated periodic syndromes. Ann Rheum Dis. 2011;70:2075-2081 pubmed publisher..MRP8/14 is a sensitive biomarker for monitoring disease activity, status of inflammation and response to IL-1 blockade in patients with CAPS. ..
- Wu R, Duan L, Ye L, Wang H, Yang X, Zhang Y, et al. S100A9 promotes the proliferation and invasion of HepG2 hepatocellular carcinoma cells via the activation of the MAPK signaling pathway. Int J Oncol. 2013;42:1001-10 pubmed publisher..These data suggest that the S100A9-induced proliferation and invasion of HepG2 cells are partly mediated by the activation of the MAPK signaling pathway. ..
- Riva M, Källberg E, Björk P, Hancz D, Vogl T, Roth J, et al. Induction of nuclear factor-?B responses by the S100A9 protein is Toll-like receptor-4-dependent. Immunology. 2012;137:172-82 pubmed publisher..Importantly, S100A9 induced stronger NF-?B activation albeit weaker cytokine secretion than LPS, suggesting that S100A9 and LPS activated NF-?B in a qualitatively distinct manner. ..
- McCormick M, Rahimi F, Bobryshev Y, Gaus K, Zreiqat H, Cai H, et al. S100A8 and S100A9 in human arterial wall. Implications for atherogenesis. J Biol Chem. 2005;280:41521-9 pubmed..S100A8 and S100A9 in atherosclerotic plaque and calcifying matrix vesicles may significantly influence redox- and Ca2+-dependent processes during atherogenesis and its chronic complications, particularly dystrophic calcification. ..
- Fontaine M, Pachot A, Larue A, Mougin B, Landelle C, Venet F, et al. Delayed increase of S100A9 messenger RNA predicts hospital-acquired infection after septic shock. Crit Care Med. 2011;39:2684-90 pubmed publisher..This biomarker may be of major interest in identifying patients with increased risk of hospital-acquired infection who could benefit from targeted therapy aimed at restoring their immune functions. ..
- Riau A, Wong T, Beuerman R, Tong L. Calcium-binding S100 protein expression in pterygium. Mol Vis. 2009;15:335-42 pubmed..The aim of this study was to investigate the presence of various S100 proteins in pterygium compared to normal conjunctiva...
- Goyette J, Geczy C. Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids. 2011;41:821-42 pubmed publisher..Conversely, S100A8 and S100A9 oxidation and S-nitrosylation may have important protective mechanisms in inflammation. ..
- Ghavami S, Eshragi M, Ande S, Chazin W, Klonisch T, Halayko A, et al. S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3. Cell Res. 2010;20:314-31 pubmed publisher..Our data indicate that S100A8/A9-promoted cell death occurs through the cross-talk of mitochondria and lysosomes via ROS and the process involves BNIP3. ..
- Frosch M, Ahlmann M, Vogl T, Wittkowski H, Wulffraat N, Foell D, et al. The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1beta form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:883-91 pubmed publisher..MRP-8/MRP-14 and IL-1beta represent a novel positive feedback mechanism activating phagocytes via 2 major signaling pathways of innate immunity during the pathogenesis of systemic-onset JIA. ..
- Maru D, Singh R, Hannah C, Albarracin C, Li Y, Abraham R, et al. MicroRNA-196a is a potential marker of progression during Barrett's metaplasia-dysplasia-invasive adenocarcinoma sequence in esophagus. Am J Pathol. 2009;174:1940-8 pubmed publisher..In conclusion, this study identified miR-196a as a potential marker of progression of BE and KRT5, SPRR2C, and S100A9 as its targets. ..
- Pili R, Haggman M, Stadler W, Gingrich J, Assikis V, Björk A, et al. Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. J Clin Oncol. 2011;29:4022-8 pubmed publisher..TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile. ..
- Vogl T, Leukert N, Barczyk K, Strupat K, Roth J. Biophysical characterization of S100A8 and S100A9 in the absence and presence of bivalent cations. Biochim Biophys Acta. 2006;1763:1298-306 pubmed..The zinc-induced tetramer is structurally very similar to the calcium-induced tetramer. Thus, like calcium, zinc acts as a regulatory factor in S100A8/S100A9-dependent signaling pathways. ..
- Atallah M, Krispin A, Trahtemberg U, Ben Hamron S, Grau A, Verbovetski I, et al. Constitutive neutrophil apoptosis: regulation by cell concentration via S100 A8/9 and the MEK-ERK pathway. PLoS ONE. 2012;7:e29333 pubmed publisher..This mechanism is suggested to have a fine-tuning role in regulating the neutrophil number in bone marrow, peripheral blood, and inflammatory sites. ..
- Burkhardt K, Schwarz S, Pan C, Stelter F, Kotliar K, Von Eynatten M, et al. Myeloid-related protein 8/14 complex describes microcirculatory alterations in patients with type 2 diabetes and nephropathy. Cardiovasc Diabetol. 2009;8:10 pubmed publisher..We investigated whether myeloid-related protein 8/14 complex (MRP8/14) secreted by transmigrating monocytes and granulocytes may represent a biomarker for microvascular alterations in patients with type 2 diabetes and nephropathy...
- De Rycke L, Baeten D, Foell D, Kruithof E, Veys E, Roth J, et al. Differential expression and response to anti-TNFalpha treatment of infiltrating versus resident tissue macrophage subsets in autoimmune arthritis. J Pathol. 2005;206:17-27 pubmed