| First Author | Hayashi S | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 6187 |
| PubMed ID | 28733636 | Mgi Jnum | J:253698 |
| Mgi Id | MGI:5926499 | Doi | 10.1038/s41598-017-06464-w |
| Citation | Hayashi S, et al. (2017) PI3K p85alpha Subunit-deficient Macrophages Protect Mice from Acute Colitis due to the Enhancement of IL-10 Production. Sci Rep 7(1):6187 |
| abstractText | We investigated the role of the PI3K p85alpha 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 p85alpha hetero-deficient (p85alpha+/-) mice compared with WT mice. The expression of proinflammatory mediators in intestinal macrophages isolated from the inflamed colonic mucosa was significantly suppressed in p85alpha+/- colitis mice compared with WT colitis mice. Interestingly, we found that bone marrow-derived macrophages (BMDMs) from p85alpha+/- mice produced a significantly higher amount of IL-10 than BMDMs from WT mice. The adoptive transfer of p85alpha+/- 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 p85alpha+/- normal colonic mucosa was significantly higher than that in the intestinal macrophages of WT normal colonic mucosa. The present results demonstrate that p85alpha+/- mice exhibit a reduced susceptibility to DSS-induced acute colitis. Our study suggests that a deficiency of PI3K p85alpha enhances the production of IL-10 in intestinal macrophages, thereby suppressing the development of DSS-induced acute colitis. |
