Intestinal epithelial BLT1 promotes mucosal repair.
Intestinal epithelial BLT1 promotes mucosal repair.
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DOI：
10.1172/jci.insight.162392
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发表时间：
2022-12-08
期刊：
影响因子：
8
通讯作者：
Nusrat, Asma
中科院分区：
文献类型：
--
作者：
Hayashi, Shusaku;Muraleedharan, Chithra K.;Oku, Makito;Tomar, Sunil;Hogan, Simon P.;Quiros, Miguel;Parkos, Charles A.;Nusrat, Asma
急性和慢性肠道炎症与上皮损伤相关，导致肠道中糜烂和溃疡形式的粘膜伤口。伤口环境中的肠上皮细胞（IEC）和免疫细胞分泌细胞因子和脂质介质以影响修复。白三烯B4（LTB 4）是一种脂质趋化因子，与其受体BLT 1结合并促进免疫细胞迁移至活动性炎症部位;然而，肠上皮BLT 1在粘膜创伤修复过程中的作用尚不清楚。在这里，我们报告说，BLT 1表达在IEC在体外和体内，在那里它作为受体不仅为LTB 4，但也为另一个配体，resolvin E1。当上皮细胞暴露于炎症微环境时，肠上皮BLT 1表达增加。使用人类和小鼠原代结肠上皮细胞，我们揭示了LTB 4/BLT 1途径促进上皮迁移和增殖，从而加速上皮创伤修复。此外，在BLT 1缺陷小鼠和骨髓嵌合体中的体内肠创伤修复实验证明了上皮BLT 1在结肠粘膜创伤修复过程中的重要贡献。综上所述，我们的研究结果显示了一个潜在的新的前修复IEC机制介导的BLT 1信号。
Acute and chronic intestinal inflammation is associated with epithelial damage, resulting in mucosal wounds in the forms of erosions and ulcers in the intestinal tract. Intestinal epithelial cells (IECs) and immune cells in the wound milieu secrete cytokines and lipid mediators to influence repair. Leukotriene B4 (LTB4), a lipid chemokine, binds to its receptor BLT1 and promotes migration of immune cells to sites of active inflammation; however, a role for intestinal epithelial BLT1 during mucosal wound repair is not known. Here we report that BLT1 was expressed in IECs both in vitro and in vivo, where it functioned as a receptor not only for LTB4 but also for another ligand, resolvin E1. Intestinal epithelial BLT1 expression was increased when epithelial cells were exposed to an inflammatory microenvironment. Using human and murine primary colonic epithelial cells, we reveal that the LTB4/BLT1 pathway promoted epithelial migration and proliferation leading to accelerated epithelial wound repair. Furthermore, in vivo intestinal wound repair experiments in BLT1-deficient mice and bone marrow chimeras demonstrated an important contribution of epithelial BLT1 during colonic mucosal wound repair. Taken together, our findings show a potentially novel prorepair in IEC mechanism mediated by BLT1 signaling.
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影响因子：
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作者：
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