巨噬细胞缺失使肠道上皮细胞易受 NSAID 诱导的损伤。
Macrophage Deficiency Makes Intestinal Epithelial Cells Susceptible to NSAID-Induced Damage.
机构信息
Department of General Surgery, Chinese PLA General Hospital, No. 28 Fuxing Rd. Beijing 100853, China.
Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
出版信息
Biomed Res Int. 2020 Nov 17;2020:6757495. doi: 10.1155/2020/6757495. eCollection 2020.
OBJECTIVES
In Crohn's disease (CD), the mechanisms underlying the regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of mucosal barrier function in the ileum are unclear. We analyzed the molecular mechanisms underlying the regulation by GM-CSF of the mucosal barrier function.
METHODS
We examined the role of GM-CSF in the intestinal barrier function in CD at the molecular-, cellular-, and animal-model levels.
RESULTS
Macrophages directly secreted GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis, which maintained intestinal barrier function. Macrophages were absent in NSAID-induced ileitis, causing GM-CSF deficiency, increasing the apoptosis rate, decreasing the proliferation rate, increasing inter- and paracellular permeabilities, decreasing the TJP levels, and reducing the numbers of mesenteric lymph nodes, memory T cells, and regulatory T cells in Csf1 transgenic mice.
CONCLUSIONS
GM-CSF is required for the maintenance of intestinal barrier function. Macrophages directly secrete GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis.
目的
在克罗恩病（CD）中，粒细胞-巨噬细胞集落刺激因子（GM-CSF）调节回肠黏膜屏障功能的机制尚不清楚。我们分析了 GM-CSF 调节黏膜屏障功能的分子机制。
方法
我们从分子、细胞和动物模型水平研究了 GM-CSF 在 CD 肠道屏障功能中的作用。
结果
巨噬细胞直接分泌 GM-CSF，促进肠上皮细胞增殖并抑制凋亡，从而维持肠道屏障功能。非甾体类抗炎药（NSAID）诱导的回肠炎中巨噬细胞缺失导致 GM-CSF 缺乏，增加了细胞凋亡率，降低了细胞增殖率，增加了细胞间和旁细胞通透性，降低了紧密连接蛋白（TJP）水平，并减少了 Csf1 转基因小鼠肠系膜淋巴结、记忆 T 细胞和调节性 T 细胞的数量。
结论
GM-CSF 是维持肠道屏障功能所必需的。巨噬细胞直接分泌 GM-CSF，促进肠上皮细胞增殖并抑制凋亡。
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