Modulation of <i>C. albicans</i>-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid

Vulvovaginal candidiasis (VVC) is a prevalent women’s infection characterized by excessive inflammation and damage of the vaginal epithelium that, in its recurrent form (RVVC), causes more than three symptomatic episodes per year, impacting nearly 8% of women globally. Current antifungal treatments...

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Main Authors: Samuele Sabbatini, Linda Zatini, Eleonora Narducci, Lucrezia Rosati, Andrea Ardizzoni, Antonella Mencacci, Mario Rende, Eva Pericolini, Francesco Galli, Desirée Bartolini, Claudia Monari
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/12/12/2455
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Summary:Vulvovaginal candidiasis (VVC) is a prevalent women’s infection characterized by excessive inflammation and damage of the vaginal epithelium that, in its recurrent form (RVVC), causes more than three symptomatic episodes per year, impacting nearly 8% of women globally. Current antifungal treatments alleviate symptoms but often fail to restore the inflammatory homeostasis of mucosal tissue and prevent recurrences. α-Tocopherol (α-TOH) and garcinoic acid (GA), a vitamin E metabolite, with immunomodulatory properties, were investigated for the first time in vaginal epithelial cells exposed to <i>C. albicans</i> infection to assess their effects on inflammatory signaling parameters important to restore cellular homeostasis. For this purpose, the protein kinases MKK3/6, p38 stress kinase (SAPK), and ERK1/2 were studied together with c-Fos transcription factor and IL-6, IL-1α, and IL-1β secretion in A-431 vaginal epithelial cells pre-treated with GA or with α-TOH and then infected with <i>C. albicans</i>. GA, differently from α-TOH, significantly reduced the <i>C. albicans</i>-induced activation of p38-SAPK while increasing pro-survival MAPK ERK1/2 activity. This resulted in a significant reduction in the secretion levels of the inflammatory cytokines IL-6 and IL-1α, as well as IL-1β. Overall, our data indicate that GA holds potential for restoring the immuno-metabolic properties of the vaginal epithelium exposed to <i>C. albicans</i> infection, which may help to treat inflammatory symptoms in VVC/RVVC.
ISSN:2076-2607