IL-4, IL-10 and IL-13 down-regulate monocyte-chemoattracting protein-1 (MCP-1) production in activated intestinal epithelial cells

Abstract

Several studies have demonstrated that intestinal epithelial cells play a major role in the initiation and perpetuation of intestinal inflammation by secreting proinflammatory cytokines and chemokines. MCP-1 is suggested to be a chemokine that plays a major part during intestinal inflammation in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4, IL-10 and IL-13 have been described to exert anti-inflammatory properties on various cell types. The aim of our study was to determine the effect of Th2 cytokines on the production of MCP-1 by activated intestinal epithelial cells. We examined Caco-2 cells as well as intestinal epithelial cells which were isolated from surgical specimens. Production of the chemokine MCP-1 was determined under stimulated and non-stimulated conditions. IL-4, IL-10 and IL-13 were added to stimulated epithelial cells under various culture conditions. Supernatants were analysed for cytokine concentrations using ELISAs. Under stimulation with physiological agents like IL-1beta or tumour necrosis factor-alpha (TNF-alpha), we observed markedly increased concentrations of MCP-1 in supernatants of Caco-2 cells and intestinal epithelial cells. IL-4, IL-10 and IL-13 all had the capacity to down-regulate the production of MCP-1 in Caco-2 cells as well as in freshly isolated epithelial cells. Caco-2 cells which were primed with Th2 cytokines 24 h before stimulation were subsequently decreased in their ability to be stimulated by IL-1beta or TNF-alpha for MCP-1 production. As MCP-1 has been shown to play a major role during intestinal inflammation, the in vitro suppression of MCP-1 in enterocytes suggests the in vivo use of regulatory cytokines in patients with active IBD.

IL-10 receptor and coreceptor expression in quiescent and activated hepatic stellate cells

“…In our study, IL-10 treatment did not affect either basal or TNF-␣-induced MCP-1 production by cultured HSC. This is in contrast to inhibition of MCP-1 production by IL-10 in activated intestinal epithelial cells (18) and inhibition of the endotoxininduced release of macrophage inflammatory protein-1 and MCP-1 by IL-10 in healthy subjects, which was shown to be independent from IL-10's inhibitory effect on TNF-␣ production (30).…”

Hydrodynamic-Based Delivery of an Interleukin-22-Ig Fusion Gene Ameliorates Experimental Autoimmune Myocarditis in Rats

“…The signal transduction pathway of IL-22 is assumed to be similar to that of IL-10 (35). IL-10 has been reported to suppress MCP-1 in IL-1-or TNF-␣-stimulated intestinal epithelial cells (36) and to inhibit IL-6 in LPS-stimulated gingival fibroblasts (37) and IL-6 and MIP-2 in TNF-␣-stimulated corneal epithelial cells and fibroblasts (38). IL-22 may act only on IL-1-stimulated cells from EAM hearts as a regulator of the expressions of these genes, similarly as IL-10.…”

Molecular Machinations: Chemokine Signals in Host-Pathogen Interactions

“…For example, the Th2-related cytokines IL-4 and IL-13 induce monocyte-derived chemokine (MDC) and C10 production in macrophages, but this is inhibited by the Th1 cytokine IFN-␥ (17,128). Cytokine regulation of chemokines also appears to be target cell specific, as illustrated by the observation that IL-4 and IL-13 strongly induce monocyte chemotactic protein 1 (MCP-1) in endothelial cells but inhibit production in epithelial cells (63,91,139). As discussed below, many microbial products can directly evoke chemokines, but the spectrum and degree of chemokines produced in response to infectious agents will be modified in part by cytokines produced during host innate and acquired immune responses.…”