IL-1β inhibits intestinal smooth muscle proliferation in an organ culture system:: involvement of COX-2 and iNOS induction in muscularis resident macrophages
IL-1β inhibits intestinal smooth muscle proliferation in an organ culture system:: involvement of COX-2 and iNOS induction in muscularis resident macrophages
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DOI：
10.1152/ajpgi.00487.2006
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发表时间：
2007-05-01
影响因子：
4.5
通讯作者：
Ozaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Ohama, Takashi;Hori, Masatoshi;Ozaki, Hiroshi
肠道炎症引起平滑肌增生，导致平滑肌层增厚，导致运动障碍。IL-1 β是一种促炎细胞因子，在肠道炎症中发挥核心作用。在这项研究中，为了评估IL-1 β对回肠平滑肌细胞增殖的影响，我们利用了器官培养系统。当大鼠回肠平滑肌组织在无血清条件下培养3天时，大多数平滑肌细胞保持其排列并保持其收缩表型。当加入10%FBS时，观察到每单位面积的平滑肌细胞数量增加。PCNA免疫组化染色显示FBS可诱导平滑肌细胞增殖。IL-1 β抑制FBS的增殖作用。此外，IL-1 β上调诱导型一氧化氮（NO）合酶和环氧合酶-2的mRNA和蛋白，从而刺激NO和PGE（2）的产生。此外，外源性NO和PGE_2抑制FBS刺激的溴脱氧尿苷阳性细胞的增加。免疫组化显示，大多数环氧合酶-2和诱导型NO合酶位于密集的巨噬细胞网络中的肌层，这是免疫反应ED 2。基于这些发现，IL-1 β作为抗增殖介质，其通过回肠平滑肌组织内驻留的巨噬细胞产生PGE（2）和NO间接起作用。
Intestinal inflammation causes hyperplasia of smooth muscle that leads to thickening of the smooth muscle layer, resulting in dysmotility. IL-1 beta is a proinflammatory cytokine that plays a central role in intestinal inflammation. In this study, to evaluate the effect of IL-1 beta on proliferation of ileal smooth muscle cells in vivo, we utilized an organ culture system. When rat ileal smooth muscle tissue was cultured under serum-free conditions for 3 days, most smooth muscle cells maintained their arrangement and kept their contractile phenotype. When 10% FBS was added, an increased number of smooth muscle cells per unit area was observed. Moreover, immunohistochemical staining for PCNA demonstrated that FBS induced proliferation of smooth muscle cells. IL-1 beta inhibited the proliferative effect of FBS. Furthermore, IL-1 beta upregulated inducible nitric oxide ( NO) synthase and cyclooxygenase- 2 mRNA and protein and thus stimulated NO and PGE(2) productions. Moreover, exogenously applied NO and PGE2 inhibited the increase of bromodeoxyuridinepositive cells stimulated with FBS. Immunostaining revealed that the majority of cyclooxygenase- 2 and inducible NO synthase was located in the dense network of macrophages resident in the muscularis, which were immunoreactive to ED2. Based on these findings, IL-1 beta acts as an anti- proliferative mediator, which acts indirectly through the production of PGE(2) and NO from resident macrophage within ileal smooth muscle tissue.