Role of mast cells in inflammatory bowel disease and inflammation-associated colorectal neoplasia in IL-10-deficient mice.
Role of mast cells in inflammatory bowel disease and inflammation-associated colorectal neoplasia in IL-10-deficient mice.
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DOI：
10.1371/journal.pone.0012220
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发表时间：
2010-08-17
期刊：
影响因子：
3.7
通讯作者：
Hale LP
中科院分区：
文献类型：
--
作者：
Chichlowski M;Westwood GS;Abraham SN;Hale LP
炎症性肠病（IBD）被假设是由于刺激免疫反应对居民肠道细菌在遗传易感的主机。肥大细胞可能在IBD发病机制中起关键作用，因为它们通常位于肠粘膜屏障下方，并且可以被细菌抗原激活。本研究探讨了肥大细胞对IBD易感的白细胞介素（IL）-10缺乏小鼠的炎症和相关肿瘤的影响。与野生型肥大细胞相比，IL-10缺陷型肥大细胞在体外组成性和触发时产生更多的促炎细胞因子。然而，尽管这种体外反应增强，肥大细胞充足的IL 10 −/−小鼠实际上降低了盲肠肿瘤坏死因子（TNF）和干扰素（IFN）-γ mRNA的表达，表明肥大细胞在体内调节炎症。肥大细胞缺乏易使Il 10 −/−小鼠发生自发性结肠炎，并导致体内肠通透性增加，先于结肠炎症的发生。然而，肥大细胞缺乏并不影响非甾体类抗炎药（NSAID）暴露引发的IBD的严重程度，或也影响肠道通透性的幽门螺杆菌感染。因此，肥大细胞似乎通过增强粘膜屏障的功效在结肠微环境中具有主要的保护作用。此外，虽然肥大细胞先前与散发性结肠癌的进展有关，但肥大细胞并不影响该炎症相关模型中结肠肿瘤的发生率或严重程度。
Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are typically located just beneath the intestinal mucosal barrier and can be activated by bacterial antigens. This study investigated effects of mast cells on inflammation and associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with and without mast cells. IL-10-deficient mast cells produced more pro-inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despite this enhanced in vitro response, mast cell-sufficient Il10 −/− mice actually had decreased cecal expression of tumor necrosis factor (TNF) and interferon (IFN)-γ mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il10 −/− mice to the development of spontaneous colitis and resulted in increased intestinal permeability in vivo that preceded the development of colon inflammation. However, mast cell deficiency did not affect the severity of IBD triggered by non-steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection that also affect intestinal permeability. Mast cells thus appear to have a primarily protective role within the colonic microenvironment by enhancing the efficacy of the mucosal barrier. In addition, although mast cells were previously implicated in progression of sporadic colon cancers, mast cells did not affect the incidence or severity of colonic neoplasia in this inflammation-associated model.
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