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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/12/12/2455 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850085127940472832 |
|---|---|
| author | Samuele Sabbatini Linda Zatini Eleonora Narducci Lucrezia Rosati Andrea Ardizzoni Antonella Mencacci Mario Rende Eva Pericolini Francesco Galli Desirée Bartolini Claudia Monari |
| author_facet | Samuele Sabbatini Linda Zatini Eleonora Narducci Lucrezia Rosati Andrea Ardizzoni Antonella Mencacci Mario Rende Eva Pericolini Francesco Galli Desirée Bartolini Claudia Monari |
| author_sort | Samuele Sabbatini |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1109799b96cc43fda0450bd5772f94ea |
| institution | DOAJ |
| issn | 2076-2607 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj-art-1109799b96cc43fda0450bd5772f94ea2025-08-20T02:43:49ZengMDPI AGMicroorganisms2076-26072024-11-011212245510.3390/microorganisms12122455Modulation of <i>C. albicans</i>-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic AcidSamuele Sabbatini0Linda Zatini1Eleonora Narducci2Lucrezia Rosati3Andrea Ardizzoni4Antonella Mencacci5Mario Rende6Eva Pericolini7Francesco Galli8Desirée Bartolini9Claudia Monari10Department of Medicine and Surgery, Medical Microbiology Section, University of Perugia, 06123 Perugia, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, ItalyDepartment of Medicine and Surgery, Medical Microbiology Section, University of Perugia, 06123 Perugia, ItalyDepartment of Medicine and Surgery, Pharmacology Division, University of Perugia, 06132 Perugia, ItalyDepartment of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, 41125 Modena, ItalyDepartment of Medicine and Surgery, Medical Microbiology Section, University of Perugia, 06123 Perugia, ItalyDepartment of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, University of Perugia, 60132 Perugia, ItalyDepartment of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, 41125 Modena, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, ItalyDepartment of Medicine and Surgery, Medical Microbiology Section, University of Perugia, 06123 Perugia, ItalyVulvovaginal 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.https://www.mdpi.com/2076-2607/12/12/2455garcinoic acid<i>C. albicans</i>vaginal cellsVVC-RVVC |
| spellingShingle | Samuele Sabbatini Linda Zatini Eleonora Narducci Lucrezia Rosati Andrea Ardizzoni Antonella Mencacci Mario Rende Eva Pericolini Francesco Galli Desirée Bartolini Claudia Monari Modulation of <i>C. albicans</i>-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid Microorganisms garcinoic acid <i>C. albicans</i> vaginal cells VVC-RVVC |
| title | Modulation of <i>C. albicans</i>-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid |
| title_full | Modulation of <i>C. albicans</i>-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid |
| title_fullStr | Modulation of <i>C. albicans</i>-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid |
| title_full_unstemmed | Modulation of <i>C. albicans</i>-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid |
| title_short | Modulation of <i>C. albicans</i>-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid |
| title_sort | modulation of i c albicans i induced immune response in vaginal epithelial cells by garcinoic acid |
| topic | garcinoic acid <i>C. albicans</i> vaginal cells VVC-RVVC |
| url | https://www.mdpi.com/2076-2607/12/12/2455 |
| work_keys_str_mv | AT samuelesabbatini modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT lindazatini modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT eleonoranarducci modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT lucreziarosati modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT andreaardizzoni modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT antonellamencacci modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT mariorende modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT evapericolini modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT francescogalli modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT desireebartolini modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid AT claudiamonari modulationoficalbicansiinducedimmuneresponseinvaginalepithelialcellsbygarcinoicacid |