PI3 Kinase p85α Subunit-Deficient Macrophages Protect Mice from DSS-Induced Acute Colitis Due to the Enhancement of Anti-Inflammatory Cytokine Production

We have recently demonstrated that phosphoinositide 3-kinase (PI3K) p85α hetero deficient (p85α+/-) mice exhibit reduced susceptibility to dextran sulfate sodium (DSS)-induced acute colitis. In the present study, we examined the role of PI3K p85α subunit in the development of acute colitis with a focus on macrophage (MΦ) functions. Experimental acute colitis was induced by giving 3% DSS in drinking water for 7 days. The severity of DSS-induced acute colitis was significantly attenuated in p85α+/- mice compared with wild-type (WT) mice. The proportion of F4/80+CD11b+MΦs in the colonic mucosa was increased equivalently in both WT and p85α+/- colitis mice. The LPS-induced mRNA expression of proinflammatory cytokines in F4/80+CD11b+MΦs isolated from the inflamed colonic mucosa was significantly suppressed in p85α+/- colitis mice compared with WT colitis mice. Interestingly, we found that bone marrow-derived MΦs (BMMΦs) from p85α+/- mice produced significantly higher amount of IL-10 in a response to LPS stimulation than BMMΦs from WT mice. Furthermore, the adoptive transfer of BMMΦs from p85α+/- mice significantly improved the severity in WT colitis mice. These results suggest that the deficiency of PI3K p85α enhances the production of IL-10 in colonic MΦs, thereby suppressing the development of DSS-induced acute colitis.