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Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition Hearps, A, Tyssen, D, Srbinovski, D, Bayigga, L, Diaz, D, Aldunate, M, Cone, R, Gugasyan, R, Anderson, D and Tachedjian, G 2017, 'Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition', Mucosal Immunology, vol. 10, no. 6, pp. 1480-1490. Document type: Journal Article Collection: Journal Articles Title Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition Author(s) Hearps, A Tyssen, D Srbinovski, D Bayigga, L Diaz, D Aldunate, M Cone, R Gugasyan, R Anderson, D Tachedjian, G Year 2017 Journal name Mucosal Immunology Volume number 10 Issue number 6 Start page 1480 End page 1490 Total pages 11 Publisher Nature Abstract Inflammation in the female reproductive tract (FRT) is associated with increased HIV transmission. Lactobacillus spp. dominate the vaginal microbiota of many women and their presence is associated with reduced HIV acquisition. Here we demonstrate that lactic acid (LA), a major organic acid metabolite produced by lactobacilli, mediates anti-inflammatory effects on human cervicovaginal epithelial cells. Treatment of human vaginal and cervical epithelial cell lines with LA (pH 3.9) elicited significant increases in the production of the anti-inflammatory cytokine IL-1RA. When added simultaneously or prior to stimulation, LA inhibited the Toll-like receptor agonist-elicited production of inflammatory mediators IL-6, IL-8, TNFα, RANTES, and MIP3α from epithelial cell lines and prevented IL-6 and IL-8 production by seminal plasma. The anti-inflammatory effect of LA was mediated by the protonated form present at pH≤3.86 and was observed with both L- and D-isomers. A similar anti-inflammatory effect of LA was observed in primary cervicovaginal cells and in an organotypic epithelial tissue model. These findings identify a novel property of LA that acts directly on epithelial cells to inhibit FRT inflammation and highlights the potential use of LA-containing agents in the lower FRT as adjuncts to female-initiated strategies to reduce HIV acquisition. Subject Biological Sciences not elsewhere classified Keyword(s) Female Reproductive-Tract Innate Immune Activation Genital-Tract Bacterial Vaginosis Gene-Expression Humanmonocytes Seminal Plasma Target-Cells Kappa-B Women DOI - identifier 10.1038/mi.2017.27 Copyright notice © 2017 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. ISSN 1933-0219 Related Links Link Description https://dx.doi.org/10.1038/mi.2017.27 Link to Published Version   Versions Version Filter Type Mon, 08 Jul 2019, 14:50:24 EST Filtered Full Citation counts:   Cited 33 times in Thomson Reuters Web of Science Article | Citations Cited 0 times in Scopus Article Altmetric details: Access Statistics: 4 Abstract Views  -  Detailed Statistics Created: Fri, 05 Jul 2019, 12:33:00 EST by Catalyst Administrator