Disease relevance of S100A9

• S100A8 and S100A9 in human arterial wall. Implications for atherogenesis [1].
• S100A9 but not S100A8 was found in macrophages in ApoE-/- murine atherosclerotic lesions, whereas both proteins are expressed in human giant cell arteritis [1].
• Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH [2].
• RESULTS: S100A8, S100A9, and RAGE were up-regulated in prostatic intraepithelial neoplasia and preferentially in high-grade adenocarcinomas, whereas benign tissue was negative or showed weak expression of the proteins [2].
• CONCLUSION: Our data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas [2].

Psychiatry related information on S100A9

• Inflammatory S100A9 and S100A12 proteins in Alzheimer's disease [3].
• In contrast to these divergent amplitude changes, the latencies of all components except P14 and frontal N18 showed progressive prolongation from the awake state to slow-wave sleep [4].
• METHOD: Plasma MIF concentrations and other standard risk factors were measured before and after participation in a diet and physical activity based weight management program [5].
• The P14 latency was significantly prolonged after sleep deprivation [6].
• Finally, L-5-HTP tends to reduce aggression, ferocity, and to a lesser extent stereotypy; MIF or piribedil, as well as reserpine, potentiates the stereotyped behaviors induced by apomorphine, whereas L-DOPA usually decreases them [7].

High impact information on S100A9

• We identified a "hinge" region mutation in C1 inhibitor with a Val to Glu replacement at P14 Val-432 [8].
• Lymphocytes from four of nine cromolyn-tolerant asthmatics demonstrated increased 3H-thymidine incorporation but none showed MIF production, whereas lymphocytes from normal subjects failed to react to cromolyn in either assay [9].
• MIF mediation of sepsis [10].
• These studies define a critical part for MIF in the pathogenesis of septic shock and identify a new target for therapeutic intervention [11].
• Consequently, Jab1-mediated rescue of fibroblasts from growth arrest is blocked by MIF [12].

Chemical compound and disease context of S100A9

• It is possible that S100A9-positive granulocytes and monocyte/macrophages may play a role in the late phase of EIU and keratitis that DEX may inhibit the migration of S100A9-positive granulocytes and monocytes from the blood into the extravascular tissues, and that nuclear factor (NF)-kappaB pathway may be involved in S100A9 expression [13].
• We investigated whether estradiol and progesterone influence MIF, IL-1beta, and TNF-alpha production in experimental colitis [14].
• Effects of EB and P on myeloperoxidase activity and MIF concentration were also assessed at 7 days in dextran sulfate sodium-induced colitis [14].
• Macrophage migration inhibitory factor (MIF), a target of sex steroids in other inflammatory models, promotes interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha release in colitis [14].
• CONCLUSION: These results suggest that cetirizine exerts its anti-inflammatory effects by inhibiting MIF as well as IL-8 production, such as those involved in inflammatory allergic skin disease, suggesting a broad spectrum of action beyond its mere H1-receptor-antagonistic function [15].

Biological context of S100A9

• The relevance of MRE is deduced from the observations that the formation of either MRE-binding complex A or MRE-binding complex B strongly correlated with S100A9 gene expression in a cell type-specific, activation- and differentiation-dependent manner [16].
• In neutrophils and monocytes the S100A8-S100A9 complex regulates phosphorylation, NADPH-oxidase activity, and fatty acid transport [1].
• S100A8 and S100A9, the Ca2+-binding neutrophil cytosolic proteins, are associated with innate immunity and regulate processes leading to leukocyte adhesion and transmigration [1].
• In this study, we report that S100A8, S100A9, and S100A8/A9 caused neutrophil chemotaxis at concentrations of 10(-12)-10(-9) M [17].
• Analysis of the S100A9 promoter in MonoMac-6 cells revealed evidence for a novel regulatory region from position -400 to -374 bp, termed myeloid-related protein regulatory element (MRE) [16].

Anatomical context of S100A9

• BACKGROUND: Calprotectin (complex of S100A8 and S100A9) is the major calcium and zinc-binding protein of phagocytes [18].
• MRP14 (S100A9) is the major calcium-binding protein of neutrophils and monocytes [19].
• Here we demonstrate S100A8 and S100A9 protein and mRNA in macrophages, foam cells, and neovessels in human atheroma [1].
• S100A8 and S100A9 are small calcium-binding proteins that are highly expressed in neutrophil and monocyte cytosol and are found at high levels in the extracellular milieu during inflammatory conditions [17].
• The pattern of S100A4 expression differed significantly from that of the proinflammatory proteins S100A9 and S100A12, which were restricted to phagocytes and granulocytes [20].

Associations of S100A9 with chemical compounds

• The two calcium-binding proteins, S100A8 and S100A9, are involved in the metabolism of arachidonic acid in human neutrophils [21].
• Matrix vesicles characterized by electron microscopy, x-ray microanalysis, nucleoside triphosphate pyrophosphohydrolase assay and cholesterol/phospholipid analysis contained predominantly S100A9 [1].
• Recombinantly expressed murine S100A9 interacts in vitro with murine and human S100A8 in an in vitro glutathione S-transferase pull-down assay [22].
• 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 [23].
• The data give strong evidence that the unique C-tail of S100A9 containing the three consecutive histidine residues (His103-His105) represents the region to which the fatty acid carboxy-group is bound to the protein complex [24].

Physical interactions of S100A9

• Failure of tetramer formation was associated with a lack of functional activity of S100A8/S100A9 complexes in promoting the formation of microtubules [25].
• Both the S100A8/S100A9 complex and S100A12 have been proven to be useful as diagnostic markers of inflammation especially in non-infectious inflammatory diseases such as arthritis, chronic inflammatory lung and bowel disease [26].
• NIF interferes with the binding of a subset of these CD11b/CD18 ligands in a highly selective manner [27].
• A single point mutation of Ser138 to Ala in the beta2 subunit abolished C3bi binding and cell adhesion but did not affect NIF binding [28].
• In addition, immunogold double-labelling experiments revealed a clear co-localization of MRP8/MRP14 complexes with the type III intermediate filament vimentin [29].

Regulatory relationships of S100A9

• S100A9 was strongly expressed in calcifying areas and the surrounding extracellular matrix [1].
• CrossLinking of the CD69 Molecule Enhances S100A9 Production in Activated Neutrophils [30].
• Furthermore, TPA-induced S100A9 gene expression in HaCaT keratinocytes was blocked after the pharmacologic inhibition of PARP-1 with 1,5-isoquinolinediol (DiQ) [31].
• These findings indicate that NIF inhibits the neutrophil-dependent endothelial injury by preventing CD11b/CD18-mediated neutrophil adhesion, but without altering the oxidant generating capacity of neutrophils interacting with the endothelial cell monolayer [32].
• Study of intracellular cytokine expression showed that MIF induced significant levels of interleukin (IL)-1 and IL-8 in monocytes and DC from UC and CD patients [33].

Other interactions of S100A9

• S100A12, MRP8, and MRP14 translocate simultaneously from the cytosol to cytoskeletal and membrane structures in a calcium-dependent manner [34].
• S100A7 and S100A9 have been shown to be markedly upregulated both in ductal carcinoma in situ of the breast and in psoriasis [35].
• S100A9 mediates neutrophil adhesion to fibronectin through activation of beta2 integrins [23].
• In addition, elevated serum levels of MRP8 and MRP14 have been found in patients suffering from a number of inflammatory disorders including cystic fibrosis, rheumatoid arthritis, and chronic bronchitis, suggesting conceivable extracellular roles for these proteins [36].
• Moreover, DNA affinity chromatography and Western blot studies indicate that a Kruppel-related zinc finger protein and the transcriptional intermediary factor 1beta (TIF1beta) are involved in an MRE-binding complex, thereby regulating the S100A9 gene expression [16].

Analytical, diagnostic and therapeutic context of S100A9

• An ELISA was applied to determine serum concentrations of S100A9 in cancer patients compared with healthy controls or to patients with benign prostatic hyperplasia (BPH) [2].
• EXPERIMENTAL DESIGN: Tissue specimens of 75 patients with organ-confined prostate cancer of different grades were analyzed by immunohistochemistry for expression of S100A8, S100A9, and RAGE [2].
• In addition, in situ hybridization of S100A8 and S100A9 was done for 20 cases [2].
• In contrast, mass spectrometric analysis and density gradient centrifugation revealed that calcium-induced association of (S100A8/S100A9)2 tetramers was strictly dependent on a functional EF-hand II in S100A9 [25].
• Furthermore, an additional protein, identified by matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) as S100A8, exhibited an increased expression in the same specimens of malignant tissues as the S100A9 protein [37].

References