We investigated the role of the PI3K p85α 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 p85α hetero-deficient (p85α+/-) mice compared with WT mice. The expression of proinflammatory mediators in intestinal macrophages 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 macrophages (BMDMs) from p85α+/- mice produced a significantly higher amount of IL-10 than BMDMs from WT mice. The adoptive transfer of p85α+/- 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 p85α+/- normal colonic mucosa was significantly higher than that in the intestinal macrophages of WT normal colonic mucosa. The present results demonstrate that p85α+/- mice exhibit a reduced susceptibility to DSS-induced acute colitis. Our study suggests that a deficiency of PI3K p85α enhances the production of IL-10 in intestinal macrophages, thereby suppressing the development of DSS-induced acute colitis.

中文翻译：

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PI3Kp85α亚基缺陷型巨噬细胞可保护小鼠免受IL-10产生增强的急性结肠炎的侵害。

我们调查了PI3Kp85α亚基在急性结肠炎发展中的作用，重点是肠道巨噬细胞。实验性急性结肠炎是在饮用水中使用3％葡聚糖硫酸钠（DSS）诱导的，持续7天。与野生型小鼠相比，在p85α杂合缺陷型（p85α+/-）小鼠中，DSS诱导的急性结肠炎的严重程度明显减轻。与野生型结肠炎小鼠相比，在p85α+/-结肠炎小鼠中，从发炎的结肠粘膜分离出的肠道巨噬细胞中促炎性介质的表达被显着抑制。有趣的是，我们发现来自p85α+/-小鼠的骨髓巨噬细胞（BMDM）产生的IL-10量显着高于来自WT小鼠的BMDM。p85α+/- BMDM的过继转移，而非WT BMDM的过继转移，显着改善了WT结肠炎小鼠的严重程度，抗IL-10抗体逆转了这种作用。此外，IL-10在p85α+/-正常结肠粘膜的肠巨噬细胞中的表达显着高于WT正常结肠粘膜的肠巨噬细胞中的IL-10的表达。目前的结果表明，p85α+/-小鼠对DSS诱导的急性结肠炎的敏感性降低。我们的研究表明，PI3Kp85α的缺乏会增加肠道巨噬细胞中IL-10的产生，从而抑制DSS诱导的急性结肠炎的发展。目前的结果表明，p85α+/-小鼠对DSS诱导的急性结肠炎的敏感性降低。我们的研究表明，PI3Kp85α的缺乏会增加肠道巨噬细胞中IL-10的产生，从而抑制DSS诱导的急性结肠炎的发展。目前的结果表明，p85α+/-小鼠对DSS诱导的急性结肠炎的敏感性降低。我们的研究表明，PI3Kp85α的缺乏会增加肠道巨噬细胞中IL-10的产生，从而抑制DSS诱导的急性结肠炎的发展。