PMID- 16674601 OWN - NLM STAT- MEDLINE DCOM- 20060731 LR - 20141120 IS - 1046-7408 (Print) IS - 1046-7408 (Linking) VI - 55 IP - 6 DP - 2006 Jun TI - Effect of toll-like receptor (TLR) agonists on TLR and microbicide expression in uterine and vaginal tissues of the mouse. PG - 434-46 AB - 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 alpha- and beta-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 beta-defensins 1, 2 and 4 and SLPI by uterine and vaginal tissues was demonstrated by RT-PCR. beta-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), Pam3Cys, Poly (I:C) or PGN] induced TLR5 and TLR9 expression but had no effect on TLR4, defensins or SLPI. Furthermore, exposure to LPS, Pam3Cys, 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. FAU - Soboll, Gisela AU - Soboll G AD - Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA. FAU - Schaefer, Todd M AU - Schaefer TM FAU - Wira, Charles R AU - Wira CR LA - eng GR - AI-13541/AI/NIAID NIH HHS/United States GR - AI-33478/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - Denmark TA - Am J Reprod Immunol JT - American journal of reproductive immunology (New York, N.Y. : 1989) JID - 8912860 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Defensins) RN - 0 (Proteinase Inhibitory Proteins, Secretory) RN - 0 (Proteins) RN - 0 (RNA, Messenger) RN - 0 (Secretory Leukocyte Peptidase Inhibitor) RN - 0 (Slpi protein, mouse) RN - 0 (Toll-Like Receptors) SB - IM MH - Animals MH - Base Sequence MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Defensins/genetics MH - Epithelial Cells/drug effects/immunology/metabolism MH - Female MH - Gene Expression/drug effects MH - Immunity, Innate MH - In Vitro Techniques MH - Mice MH - Mice, Inbred BALB C MH - Proteinase Inhibitory Proteins, Secretory MH - Proteins/genetics MH - RNA, Messenger/genetics/metabolism MH - Secretory Leukocyte Peptidase Inhibitor MH - Toll-Like Receptors/*agonists/genetics/*metabolism MH - Uterus/*drug effects/*immunology/metabolism MH - Vagina/*drug effects/*immunology/metabolism EDAT- 2006/05/06 09:00 MHDA- 2006/08/01 09:00 CRDT- 2006/05/06 09:00 PHST- 2006/05/06 09:00 [pubmed] PHST- 2006/08/01 09:00 [medline] PHST- 2006/05/06 09:00 [entrez] AID - AJI381 [pii] AID - 10.1111/j.1600-0897.2006.00381.x [doi] PST - ppublish SO - Am J Reprod Immunol. 2006 Jun;55(6):434-46. doi: 10.1111/j.1600-0897.2006.00381.x.