Microbial compounds induce the expression of pro-inflammatory cytokines, chemokines and human β-defensin-2 in vaginal epithelial cells

• Published in: Microbes and infection 2005-07, Vol.7 (9), p.1117-1127
• Main Authors: Pivarcsi, Andor, Nagy, Istvan, Koreck, Andrea, Kis, Kornelia, Kenderessy-Szabo, Anna, Szell, Marta, Dobozy, Attila, Kemeny, Lajos
• Format: Article
• Language: English
• Subjects: Antimicrobial peptides; beta-Defensins - biosynthesis; Biological and medical sciences; Candida albicans; Candida albicans - immunology; Cell Line; Chemokines - biosynthesis; Cytokines - biosynthesis; Epithelial Cells - drug effects; Epithelial Cells - immunology; Female; Female reproductive tract; Fundamental and applied biological sciences. Psychology; Fungal infections; Gene Expression; Humans; Immunohistochemistry; Innate immunity; Lipopolysaccharides - immunology; Microbiology; NF-kappa B - analysis; Peptidoglycan - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Toll-Like Receptor 2 - analysis; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 4 - analysis; Toll-Like Receptor 4 - genetics; Toll-like receptors (TLRs); Vagina - drug effects; Vagina - immunology; Zymosan - immunology
• ISSN: 1286-4579; 1769-714X; 1769-714X
• DOI: 10.1016/j.micinf.2005.03.016

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-α and IL-8/ CXCL8 in vaginal epithelial cells. Furthermore, the expression and production of human β-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-κB 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.