A: Isolated colonic lamina propria macrophages from the large intestine were incubated with or without heat-killed Streptococcus sp. for 16 hours. mRNA of cells from Mgl1+/+ and … Discussion The hallmark of inflammatory bowel diseases, www.selleckchem.com/products/AZD2281(Olaparib).html including Crohn��s disease and ulcerative colitis, is abnormal inflammation of the gastrointestinal tract, but the pathogenesis has not been fully elucidated. In the present study, Mgl1-deficient mice exhibited a more severe inflammation than wild-type mice in an experimental model for ulcerative colitis. The mechanistic basis for this difference was determined to be a change in cytokine production in response to intestinal commensal bacteria. The predominant portion of cells expressing MGL1 in colonic lamina propria were found to be macrophages, and these cells were shown to produce IL-10 in response to the bacteria.

IL-10 was previously considered a crucial cytokine for the maintenance of intestinal homeostasis because IL-10-deficient mice spontaneously developed colitis.5 The present study clearly shows that lamina propria macrophages lacking Mgl1 produced less IL-10 than these cells expressing MGL1. IL-10 produced by a variety of cells, such as macrophages, DCs, and T cells, plays an important role in the pathogenesis of colitis. In macrophage-depleted mice, DSS-induced colitis was more severe, and IL-10 mRNA from the whole colon of these mice was decreased compared with sham-treated mice, indicating that colonic macrophages secrete IL-10 during colonic inflammation.29 However, the most important target of IL-10 remains unclear.

IL-10 is likely to influence the functions of a wide range of immune cell populations by suppressing pro-inflammatory responses.29 For example, IL-10 is known to suppress production of IL-12, tumor necrosis factor-��, and reactive oxygen species by macrophages and DCs. It also inhibits Th1 and Th2 responses, which aggravate pathogenic inflammation. Colonic epithelial cells are not likely to act as the target of IL-10. IL-10 has been shown to inhibit MHC class II expression on epithelial cell lines, but it does not affect the chemokine secretion responsible for the recruitment of neutrophils and monocytes to injured sites.30,31 By immunohistochemical analysis, MGL1-expressing cells were observed in the lamina propria and in the submucosa, where many other types of immune cells were also observed.

After the induction of colitis, cells expressing MGL1 were absent from this area. Although it is possible that cells expressing MGL1 migrated to other regions, it is likely that MGL1 expression was down-modulated on CD11b+cells, considering that CD11b+ cells with similar morphology were present in this ulcerated region. Furthermore, when isolated lamina propria macrophages were exposed to heat-killed Batimastat Streptococcus sp., these cells significantly reduced the cell surface expression of MGL1, as indicated by the binding of monoclonal antibody LOM-8.