Commensal-Epithelial Signaling Mediated via Formyl Peptide Receptors
Commensal-Epithelial Signaling Mediated via Formyl Peptide Receptors
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DOI：
10.2353/ajpath.2010.100529
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发表时间：
2010-12-01
影响因子：
6
通讯作者：
Neish, Andrew S.
中科院分区：
文献类型：
--
作者：
Wentworth, Christy C.;Jones, Rheinallt M.;Neish, Andrew S.
共生细菌和/或其产物对哺乳动物肠道产生有益的影响，包括刺激生理细胞更新和增强伤口愈合，而不激活明显的炎症。在本研究中，我们观察到共生细菌介导肠上皮细胞中非炎症细胞外信号调节激酶[ERK]/丝裂原激活蛋白激酶和Ala信号通路的激活，并描述了这种细菌激活信号传导的机制。所有测试的共生细菌菌株均诱导ERK磷酸化，而不刺激促炎性磷酸-I kappa B 或促凋亡 phos pho-c Jun NH2 末端激酶，其中乳杆菌属最有效。使用肽 N 甲酰基 Met Leu Phe 重现了这种信号激活模式，这是一种已知可刺激哺乳动物吞噬细胞中信号传导事件的细菌产物。肠上皮细胞对 N 甲酰基 Met Leu Phe 的感知是通过位于质膜中最近表征的甲酰基肽受体发生的。共生细菌和 N 甲酰基 Met Leu Phe 应用于极化肠上皮细胞的顶端表面导致了特异性甲酰基肽受体激活。此外，用 Boc2（一种特定的肽拮抗剂）或百日咳毒素（一种 G(1) 蛋白抑制剂）预处理模型上皮和小鼠结肠，消除了共生介导的 ERK 磷酸化。综上所述，这些数据表明共生细菌以甲酰基肽受体依赖性方式特异性激活 ERK/丝裂原激活蛋白激酶途径，描绘了共生细菌参与肠道上皮细胞信号传导的机制。 (Am J Pathol 2010 177 2782-2790 DOI 10 2353/ajpath 2010 100529)
Commensal bacteria and/or their products engender beneficial effects to the mammalian gut including stimulating physiological cellular turnover and enhancing wound healing without activating overt inflammation In the present study we observed commensal bacteria mediated activation of the noninflammatory extracellular signal regulated kinase[ERK]/mitogen activated protein kinase and Ala signaling pathways in gut epithelial cells and delineated a mechanism for this bacterially activated signaling All tested strains of commensal bacteria induced ERK phosphorylation without stimulating pro-inflammatory phospho-I kappa B or pro-apoptotic phos pho-c Jun NH2 terminal kinase with Lactobacillus species being most potent. This pattern of signaling activation was recapitulated using the peptide N formyl Met Leu Phe a bacterial product known to stimulate signaling events in mammalian phagocytes Sensing of N formyl Met Leu Phe by gut epithelial cells occurs via recently characterized formyl peptide receptors located in the plasma membrane Both commensal bacteria and N formyl Met Leu Phe application to the apical surface of polarized gut epithelial cells resulted in specific formyl peptide receptor activation. In addition, pretreatment of model epithelia and murine colon with Boc2 (a specific peptide antagonist) or pertussis toxin (a G(1) protein inhibitor) abolished commensal mediated ERK phosphorylation Taken together these data show that commensal bacteria specifically activate the ERK/mitogen activated protein kinase pathway in an formyl peptide receptor-dependent manner delineating a mechanism by which commensal bacteria con tribute to cellular signaling in gut epithelia. (Am J Pathol 2010 177 2782-2790 DOI 10 2353/ajpath 2010 100529)