Enteroendocrine cells express functional Toll-like receptors
Enteroendocrine cells express functional Toll-like receptors
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DOI：
10.1152/ajpgi.00249.2006
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发表时间：
2007-06-01
影响因子：
4.5
通讯作者：
Plevy, Scott E.
中科院分区：
文献类型：
--
作者：
Bogunovic, Milena;Dave, Shaival H.;Plevy, Scott E.
肠上皮细胞（IEC）提供了针对肠道微生物植物群的物理和免疫屏障。Toll样受体（TLR）通过与保守的微生物模式相互作用，激活先天免疫系统细胞中的炎性基因表达。以前对IEC中TLR的表达和功能的研究报道了不同的结果。因此，在人和鼠肠切片中表征TLR表达，并在IEC系中测试TLR功能。TLR 1、TLR 2和TLR 4共表达于主要位于肠隐窝且属于肠内分泌谱系的人和鼠IEC亚群上。肠内分泌细胞（EEC）系表现出与原代细胞相似的TLR表达模式。用特异性TLR配体：LPS或合成细菌脂蛋白激活鼠EEC系STC-1。在用细菌配体刺激的STC-1细胞中，证实NF-κ B和MAPK活化。诱导TNF和巨噬细胞抑制蛋白-2的表达。此外，细菌配体诱导抗炎基因转化生长因子-β的表达。LPS可引起STC-1细胞内钙流增加，使CCK分泌迅速增加。最后，STC-1细胞的条件培养基抑制了活化的巨噬细胞产生一氧化氮和IL-12 p40。总之，表达TLR的人和鼠IEC属于肠内分泌谱系。使用鼠EEC模型，证明了TLR活化的广泛功能效应。这项研究表明，EECs在先天免疫反应中的潜在作用。
Intestinal epithelial cells ( IECs) provide a physical and immunological barrier against enteric microbial flora. Toll- like receptors ( TLRs), through interactions with conserved microbial patterns, activate inflammatory gene expression in cells of the innate immune system. Previous studies of the expression and function of TLRs in IECs have reported varying results. Therefore, TLR expression was characterized in human and murine intestinal sections, and TLR function was tested in an IEC line. TLR1, TLR2, and TLR4 are coexpressed on a subpopulation of human and murine IECs that reside predominantly in the intestinal crypt and belong to the enteroendocrine lineage. An enteroendocrine cell ( EEC) line demonstrated a similar expression pattern of TLRs as primary cells. The murine EEC line STC-1 was activated with specific TLR ligands: LPS or synthetic bacterial lipoprotein. In STC-1 cells stimulated with bacterial ligands, NF-kappa B and MAPK activation was demonstrated. Furthermore, the expression of TNF and macrophage inhibitory protein-2 were induced. Additionally, bacterial ligands induced the expression of the anti-inflammatory gene transforming growth factor-beta. LPS triggered a calcium flux in STC-1 cells, resulting in a rapid increase in CCK secretion. Finally, conditioned media from STC-1 cells inhibited the production of nitric oxide and IL-12 p40 by activated macrophages. In conclusion, human and murine IECs that express TLRs belong to the enteroendocrine lineage. Using a murine EEC model, a broad range of functional effects of TLR activation was demonstrated. This study suggests a potential role for EECs in innate immune responses.