Adipose-derived stem cells ameliorate colitis by suppression of inflammasome formation and regulation of M1-macrophage population through prostaglandin E2
Adipose-derived stem cells ameliorate colitis by suppression of inflammasome formation and regulation of M1-macrophage population through prostaglandin E2
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DOI：
10.1016/j.bbrc.2018.03.096
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发表时间：
2018-04-15
影响因子：
3.1
通讯作者：
Kim, Hyun-Soo
中科院分区：
文献类型：
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作者：
Park, Hong Jun;Kim, Jiye;Kim, Hyun-Soo
炎症性肠病（IBD）是一种特发性疾病，由具有遗传易感性的个体对肠道微生物的免疫应答失调引起。因此，减轻炎症对治疗IBD非常重要。间充质干细胞（MSC）已被强调为基于其免疫调节特性的治疗自身免疫性疾病的新候选者。本研究采用THP-1巨噬细胞和葡聚糖硫酸钠（DSS）诱导的小鼠慢性结肠炎模型，探讨脂肪组织来源的间充质干细胞（ASCs）的抗炎机制和治疗作用。LPS处理的THP-1细胞在第2天表达M1巨噬细胞标志物CD 11b的mRNA。然而，与ASC共培养的THP-1表达M2巨噬细胞标志物CD 206、CD 68、CCL 18、legumain和IL-10的mRNA。在与ASC共培养的THP-1细胞中，与LPS处理的THP-1细胞相比，前体（pro）-IL-1 β、考克斯-2和NLRP 3显著增加。ASCs显著抑制IL-1 β和IL-18的分泌，但在THP-1和ASCs的共培养条件下，PGE 2的产生高度增加。PGE 2处理抑制IL-18分泌，并且PGE 2抑制THP-1细胞中炎性小体复合物（ASC/Cas-1/NLRP 3）的形成。在DSS诱导的慢性结肠炎模型中，ASC通过减少巨噬细胞总数和M1巨噬细胞群来改善结肠炎。我们的研究结果表明，ASCs可以通过控制巨噬细胞群体来抑制炎症反应，并且ASCs可能对IBD的治疗有用。(C)2018爱思唯尔公司All rights reserved.
Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to intestinal microbes in an individual with a genetic predisposition. Therefore, alleviation of inflammation is very important to treat IBD. Mesenchymal stem cells (MSCs) have been highlighted as new candidates for treating autoimmune disease based on their immunomodulatory properties. In this study, we investigated the anti-inflammatory mechanism and therapeutic effects of adipose tissue-derived MSCs (ASCs) using THP-1 macrophages and dextran sodium sulfate (DSS)-induced mice with chronic colitis. LPS-treated THP-1 cells expressed mRNA of CD11b, an M1 macrophage marker, at day 2. However, THP-1 co-cultured with ASCs expressed mRNA of CD206, CD68, CCL18, legumain, and IL-10, markers of M2 macrophages. In THP-1 cells co-cultured with ASCs, precursor (pro)-IL-1 beta, Cox-2, and NLRP3 increased dramatically compared to LPS-treated THP-1 cells. Secretion of IL-1 beta and IL-18 was significantly inhibited by ASCs, but PGE2 production was highly increased in co-culture conditions of THP-1 and ASCs. IL-18 secretion was inhibited by PGE2 treatment, and PGE2 inhibited inflammasome complex (ASC/Cas-1/NLRP3) formation in THP-1 cells. In the DSS-induced chronic colitis model, ASCs ameliorated colitis by decreasing the total number of macrophages and the M1 macrophage population. Our results suggest that ASCs can suppress the inflammatory response by controlling the macrophage population, and ASCs may be therapeutically useful for the treatment of IBD. (C) 2018 Elsevier Inc. All rights reserved.