PI3K p85α Subunit-deficient Macrophages Protect Mice from Acute Colitis due to the Enhancement of IL-10 Production

We investigated the role of the PI3K p85 alpha subunit in the development of acute colitis with a focus on intestinal macrophages. Experimental acute colitis was induced using 3% dextran sulfate sodium (DSS) in drinking water for 7 days. The severity of DSS-induced acute colitis was significantly attenuated in p85 alpha hetero-deficient (p85 alpha+/-) mice compared with WT mice. The expression of proinflammatory mediators in intestinal macrophages isolated from the inflamed colonic mucosa was significantly suppressed in p85 alpha+/-colitis mice compared with WT colitis mice. Interestingly, we found that bone marrow-derived macrophages (BMDMs) from p85 alpha+/-mice produced a significantly higher amount of IL-10 than BMDMs from WT mice. The adoptive transfer of p85 alpha+/-BMDMs, but not WT BMDMs, significantly improved the severity in WT colitis mice, and this effect was reversed by anti-IL-10 antibody. Furthermore, the expression of IL-10 in the intestinal macrophages of p85 alpha+/-normal colonic mucosa was significantly higher than that in the intestinal macrophages of WT normal colonic mucosa. The present results demonstrate that p85 alpha+/-mice exhibit a reduced susceptibility to DSS-induced acute colitis. Our study suggests that a deficiency of PI3K p85 alpha enhances the production of IL-10 in intestinal macrophages, thereby suppressing the development of DSS-induced acute colitis.