TLR4 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
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TLR4 activation in endometrial stromal cells increases IL-8 secretion, which in turn enhances cell invasion and proliferation via FAK signaling.
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Abstract
PROBLEM: Chronic inflammation is important for the occurrence of endometriosis, but the molecular mechanisms are still poorly understood. TLR4 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 TLR4 in normal, eutopic endometrium, and ectopic tissues was analyzed by immunohistochemistry. The expression of the key molecules in endometrial stromal cells (ESCs) was assessed by in-cell Western assays. The invasion of eutopic ESCs from patients with endometriosis was evaluated by Matrigel invasion assay. The effects of CXCL8 on the proliferation of ESCs in vitro were assessed using BrdU assays. RESULTS: We found that the expression of TLR4 is higher in the eutopic endometrium than the normal endometrium and that ectopic tissue had the highest level of expression. TLR4 activation stimulated IL-8 secretion and the expression of its receptor CXCR1 in ESCs by activating p38/ERK, but not JNK and NK-κB signal pathways. IL-8 could enhance the invasion and proliferation of ESCs through the FAK signal pathway, and these effects could be abolished by an anti-CXCL8 neutralizing antibody or by a FAK inhibitor.
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Cited by (11)
- Research Advances in the Pathogenesis of Inflammatory Factors and Adenomyosis 2025
- CXC chemokines influence immune surveillance in immunological disorders: Polycystic ovary syndrome and endometriosis 2023
- Endometrial receptivity in adenomyosis and the role of signaling pathways in the pathogenesis of the disease (literature review) 2022
- A systematic review of toll-like receptors in endometriosis 2021
- Co-morbidity of type 1 diabetes and endometriosis: bringing a new paradigm into focus 2019
- Role of interleukin-32 in the pathogenesis of endometriosis: in vitro, human and transgenic mouse data 2018
- Avaliação da participação dos <i>Mollicutes</i> e outros microrganismos de interesse genital na endometriose humana. 2017
- The Expression of Toll-like receptors in eutopic and ectopic endometrium and its implication in the inflammatory pathogenesis of adenomyosis 2017
- The extracellular signal‐regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation 2017
- Fractalkine/<scp>CX</scp>3<scp>CR</scp>1 is involved in the pathogenesis of endometriosis by regulating endometrial stromal cell proliferation and invasion 2016
- Hypoxia-inducible factor-1alpha: A promising therapeutic target in endometriosis 2016
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