Phagocyte‐specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease

Abstract

Phagocyte-derived S100 proteins are endogenous activators of innate immune responses. S100A12 binds to the receptor for advanced glycation end-products, while complexes of S100A8/S100A9 (myeloid-related proteins, MRP8/14; calprotectin) are ligands of toll-like receptor 4. These S100 proteins can be detected in stool. In the present study we analyse the release of S100A12 and MRP8/14 from intestinal tissue. Specimens from patients with Crohn's disease (CD; n = 30), ulcerative colitis (UC; n = 30), irritable bowel syndrome (IBS; n = 30) or without inflammation (n = 30) were obtained during endoscopy. After 24 h culture, S100A12 and MRP8/14 were analysed in supernatants. Endoscopic, histological, laboratory and clinical disease activity measures were documented. We found an increased spontaneous release of S100A12 from tissue in inflammatory bowel disease (IBD). The release of S100A12 into the supernatants was 28-fold enhanced in inflamed tissue when compared to non-inflamed tissue (mean 46.9 vs. 1.7 ng/ml, p < 0.0001). In active CD, release of S100A12 and MRP8/14 was strongly dependent on localization, with little release from sites of active ileal inflammation compared to colonic inflammation. This difference was more pronounced for S100A12 than for MRP8/14. S100A12 and MRP8/14 provoked up-regulation of adhesion molecules and chemokines on human intestinal microvascular endothelial cells (HIMECs) isolated from normal colonic tissue. The direct release of phagocyte-derived S100 proteins from inflamed tissues may reflect secretion from infiltrating neutrophils (S100A12) and also monocytes or epithelial cells (MRP8/14). Via activation of pattern recognition receptors, these proteins promote inflammation in intestinal tissue. The enhanced mucosal release can explain the correlation of fecal markers with disease activity in IBD.

Increased Levels of Calprotectin in Obesity Are Related to Macrophage Content: Impact on Inflammation and Effect of Weight Loss

“…In line with these functions, phagocytes reportedly express S100A8 and S100A9 under multiple inflammatory conditions, i.e., inflammatory bowel disease, rheumatoid arthritis or allograft rejection (8)(9)(10), whereas numerous pathological conditions associated with inflammation in humans are associated with elevated S100A8 and S100A9 levels (11). Furthermore, the inflammatory factors interleukin (IL)-1, interferon (IFN)-γ and tumor necrosis factor (TNF)-α induce the expression and secretion of the S100A8/A9 heterodimer (12)(13)(14).…”

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

“…Although the role of this protein in zebrafish is still unknown, S100 proteins are endogenous activators of innate immune responses in mammals, and some of them have proinflammatory properties and are associated with different inflammatory diseases, such as inflammatory bowel disease. [82][83][84] Several genes involved in the relief of oxidative stress as a compensatory mechanism were up-modulated in tolerized zebrafish as described for mammals 85,86 ; these include glutathione peroxidase 7 (GPX7), which mitigates the organ dysfunction during chronic inflammation, and phosphoenolpyruvate synthase, which is an essential enzyme when pyruvate and lactate are used as a carbon source. The upmodulation in tolerized fish suggests a mechanism for avoiding the excess of lactate and hypoxia that induces the organ failure associated with sepsis.…”

Vaginal Epithelial Cell-Derived S100 Alarmins Induced by Candida albicans via Pattern Recognition Receptor Interactions Are Sufficient but Not Necessary for the Acute Neutrophil Response during Experimental Vaginal Candidiasis

“…Furthermore, the study revealed that S100 alarmins were produced by vaginal epithelial cells following interaction with C. albicans. S100 alarmins are cytosolic and secretory proteins produced by a variety of cell types, including PMNs, monocytes, and epithelial cells (14)(15)(16)(17)(18). In VVC, epithelial cell-derived S100 alarmins are suggested to be secreted in response to C. albicans as an initial signal for PMN migration, which becomes amplified further by subsequent production via recruited PMNs in the vaginal cavity.…”