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Effect of Toll‐Like Receptor (TLR) Agonists on TLR and Microbicide Expression in Uterine and Vaginal Tissues of the Mouse
Author(s) -
Soboll Gisela,
Schaefer Todd M.,
Wira Charles R.
Publication year - 2006
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/j.1600-0897.2006.00381.x
Subject(s) - microbicide , toll like receptor , vaginal microbicide , receptor , toll , uterus , pharmacology , biology , medicine , endocrinology , immunology , innate immune system , microbicides for sexually transmitted diseases , health services , population , environmental health , human immunodeficiency virus (hiv)
Problem Epithelial cells lining the uterine lumen are the first line of defense against pathogenic microbes. The objective of this study was to examine the expression of Toll‐like receptors (TLRs), defensins and secretory leukocyte protease inhibitor (SLPI) in the mouse uterus and vagina and in primary uterine epithelial cells and to determine whether TLR agonists induce TLR and defensin expression. Method of study The mRNA expression of α ‐ and β ‐defensins (AD1, 2 and 5 and BD1, 2 and 4) and SLPI was examined by real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) along with the secretion of macrophage chemotactic protein‐1 (MCP‐1), measured by enzyme‐linked immunosorbent assay. Results Expression of TLR1–9 as well as β ‐defensins 1, 2 and 4 and SLPI by uterine and vaginal tissues was demonstrated by RT‐PCR. β ‐Defensins and SLPI expression was greater in the vagina than in the uterus. Comparison of fresh and polarized uterine epithelial cells indicated that TLR2–6 expression was unaffected by culture. Incubation of polarized epithelial cells with TLR agonists [lipopolysaccharide (LPS), Pam 3 Cys, Poly (I:C) or PGN] induced TLR5 and TLR9 expression but had no effect on TLR4, defensins or SLPI. Furthermore, exposure to LPS, Pam 3 Cys, Poly (I:C) or PGN, induced MCP‐1 secretion by polarized epithelial cells in culture. Conclusion These results indicate that the uterus and vagina as well as uterine epithelial cells are responsive to bacterial and viral pathogens. Not only do epithelial cells respond to TLR agonists by releasing MCP‐1, which mediates inflammatory responses, but they also influence the expression of selected TLR genes to further enhance innate immune protection.