Research Output
Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFkappaB activation resulting in a microenvironment predisposed to ectopic pregnancy
  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.

  • Type:

    Article

  • Date:

    23 September 2010

  • Publication Status:

    Published

  • DOI:

    10.1016/j.ajpath.2010.11.019

  • ISSN:

    0002-9440

  • Library of Congress:

    RG Gynecology and obstetrics

  • Dewey Decimal Classification:

    618 Gynecology, obstetrics, pediatrics & geriatrics

Citation

Shaw, J. L. V., Wills, G. S., Lee, K., Horner, P. J., McClure, M. O., Abrahams, V. M., …Horne, A. W. (2011). Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFkappaB activation resulting in a microenvironment predisposed to ectopic pregnancy. American Journal of Pathology, 178(1), 253-60. https://doi.org/10.1016/j.ajpath.2010.11.019

Authors

Keywords

Chlamydia trachomatis, ectopic pregnancy,

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