Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFκB activation resulting in a microenvironment predisposed to ectopic pregnancy

Shaw, Julie L V; Wills, Gillian S; Lee, Kai-Fai; Horner, Paddy J; McClure, Myra O; Abrahams, Vikki M; Wheelhouse, Nick; Jabbour, Henry N; Critchley, Hilary O D; Entrican, Gary; Horne, Andrew W

Abstract

Chlamydia trachomatis and smoking are major risk factors for tubal ectopic pregnancy (EP), but the underlying mechanisms of these associations are not completely understood. Fallopian tube (FT) from women with EP exhibit altered expression of prokineticin receptors 1 and 2 (PROKR1 and PROKR2); smoking increases FT PROKR1, resulting in a microenvironment predisposed to EP. We hypothesize that C. trachomatis also predisposes to EP by altering FT PROKR expression and have investigated this by examining NFkappaB activation via ligation of the Toll-like receptor (TLR) family of cell-surface pattern recognition receptors. PROKR2 mRNA was higher in FT from women with evidence of past C. trachomatis infection than in those without (P < 0.05), and was also increased in FT explants and in oviductal epithelial cell line OE-E6/E7 infected with C. trachomatis (P < 0.01) or exposed to UV-killed organisms (P < 0.05). The ability of both live and dead organisms to induce this effect suggests ligation of a cell-surface-expressed receptor. FT epithelium and OE-E6/E7 were both found to express TLR2 and TLR4 by immunohistochemistry. Transfection of OE-E6/E7 cells with dominant-negative TLR2 or IkappaBalpha abrogated the C. trachomatis-induced PROKR2 expression. We propose that ligation of tubal TLR2 and activation of NFkappaB by C. trachomatis leads to increased tubal PROKR2, thereby predisposing the tubal microenvironment to ectopic implantation.

• Journal Article Type: Article
• Acceptance Date: Sep 28, 2010
• Online Publication Date: Sep 23, 2010
• Publication Date: 2011-01
• Deposit Date: Jul 21, 2016
• Publicly Available Date: Mar 10, 2020
• Journal: American Journal of Pathology
• Print ISSN: 0002-9440
• Electronic ISSN: 1525-2191
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 178
• Issue: 1
• Pages: 253-260
• DOI: https://doi.org/10.1016/j.ajpath.2010.11.019
• Keywords: Chlamydia trachomatis, ectopic pregnancy,
• Public URL: http://researchrepository.napier.ac.uk/Output/304737
• Related Public URLs: http://ac.els-cdn.com/S0002944010000659/1-s2.0-S0002944010000659-main.pdf?_tid=d0d44a94-b5e8-11e5-9f24-00000aacb360&acdnat=1452244904_c154af75f7504269a4af6f51961714d5