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TLR 4 Activation Promotes the Secretion of IL ‐8 Which Enhances the Invasion and Proliferation of Endometrial Stromal Cells in an Autocrine Manner via the FAK Signal Pathway
Author(s) -
Luo Xuezhen,
Zhou Wenjie,
Tao Yu,
Wang Xiaoqiu,
Li Dajin
Publication year - 2015
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12425
Subject(s) - stromal cell , autocrine signalling , matrigel , cancer research , endometrium , signal transduction , tlr4 , biology , microbiology and biotechnology , mapk/erk pathway , receptor , medicine , endocrinology , angiogenesis
Problem Chronic inflammation is important for the occurrence of endometriosis, but the molecular mechanisms are still poorly understood. TLR 4 is not only expressed on immune cells but is also present in the human endometrium, and its regulation might be crucial for the pathogenesis of endometriosis. Method of study In this study, the expression of TLR 4 in normal, eutopic endometrium, and ectopic tissues was analyzed by immunohistochemistry. The expression of the key molecules in endometrial stromal cells ( ESC s) was assessed by in‐cell Western assays. The invasion of eutopic ESC s from patients with endometriosis was evaluated by Matrigel invasion assay. The effects of CXCL 8 on the proliferation of ESC s in vitro were assessed using BrdU assays. Results We found that the expression of TLR 4 is higher in the eutopic endometrium than the normal endometrium and that ectopic tissue had the highest level of expression. TLR 4 activation stimulated IL ‐8 secretion and the expression of its receptor CXCR 1 in ESC s by activating p38/ ERK , but not JNK and NK ‐κB signal pathways. IL ‐8 could enhance the invasion and proliferation of ESC s through the FAK signal pathway, and these effects could be abolished by an anti‐ CXCL 8 neutralizing antibody or by a FAK inhibitor.