Microbial compounds induce the expression of pro-inflammatory cytokines, chemokines and human beta-defensin-2 in vaginal epithelial cells.
Vaginal epithelium has a powerful innate immune system that protects the female reproductive organs from bacterial and fungal infections. In the present study, we aimed to explore whether the Toll-like receptor (TLR) signaling pathway and the induction of pro-inflammatory cytokines and antimicrobial peptides could contribute to the protection against pathogenic microorganisms in vaginal epithelia, using an immortalized vaginal epithelial cell line PK E6/E7 as a model. We found that TLR2 and TLR4 receptors are expressed in vivo in the vaginal epithelia and in vitro in PK E6/E7 vaginal epithelial cell line. The Gram-negative cell wall compound lipopolysaccharide (LPS), the Gram-positive compound peptidoglycan (PGN), heat-killed Candida albicans and zymosan significantly (P<0.05) induced the expression of pro-inflammatory cytokines and chemokines such as TNF-alpha and IL-8/CXCL8 in vaginal epithelial cells. Furthermore, the expression and production of human beta-defensin-2 (hBD2), an antimicrobial peptide with chemotactic functions, was also up-regulated in PK E6/E7 cells after treatment with LPS, PGN or C. albicans. Treatment of vaginal epithelial cells with microbial compounds induced the activation and nuclear translocation of NF-kappaB transcription factor, a key element of innate and adaptive immune responses. In our work, we provide evidence that microbial compounds induce the production of pro-inflammatory cytokines, chemokines and antimicrobial peptides in vaginal epithelial cells. In vivo, vaginal epithelial cell-derived inflammatory mediators and antimicrobial peptides may play important roles in vaginal immune responses and in the elimination of pathogens from the female reproductive tract.
Pivarcsi
Andor
A
Dermatological Research Group of the Hungarian Academy of Sciences, University of Szeged, Koranyi fasor 6., 6701 Szeged, Hungary. andor@mail.derma.szote.u-szeged.hu
Nagy
Istvan
I
Koreck
Andrea
A
Kis
Kornelia
K
Kenderessy-Szabo
Anna
A
Szell
Marta
M
Dobozy
Attila
A
Kemeny
Lajos
L
D002176:Candida albicans / Q000276:immunology; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000276:immunology; D016328:NF-kappa B / Q000032:analysis; D010457:Peptidoglycan / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000032:analysis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000235:genetics; D014621:Vagina / Q000187:drug effects / Q000276:immunology*; D015054:Zymosan / Q000276:immunology; D023083:beta-Defensins / Q000096:biosynthesis*
D018925:Chemokines; D016207:Cytokines; C106641:DEFB4A protein, human; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010457:Peptidoglycan; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D023083:beta-Defensins; D015054:Zymosan