title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital & Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Xue-zhen
authors.initials: XZ
authors.lastname: Luo
authors.affiliation: Laboratory for Reproductive Immunology, Hospital & Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Zhou
authors.affiliation: Laboratory for Reproductive Immunology, Hospital & Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Laboratory for Reproductive Immunology, Hospital & Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Xiao-qiu
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital & Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai, China.|Department of Obstetrics and Gynecology, Hainan Medical College Affiliated Hospital, Haikou, China.
authors.forename: Da-jin
authors.initials: DJ
authors.lastname: Li
mesh_terms: D000328:Adult; D019898:Autocrine Communication; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002828:Choristoma; D004715:Endometriosis / Q000276:immunology*; D004717:Endometrium / Q000473:pathology*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016209:Interleukin-8; D051197:Toll-Like Receptor 4; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: Endometrial stromal cells; FAK signal pathway; IL-8; TLR4; endometriosis