Sabbatini Samuele, Zatini Linda, Narducci Eleonora, Rosati Lucrezia, Ardizzoni Andrea, Mencacci Antonella, Rende Mario, Pericolini Eva, Galli Francesco, Bartolini Desirée, Monari Claudia
Department of Medicine and Surgery, Medical Microbiology Section, University of Perugia, 06123 Perugia, Italy.
Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy.
Microorganisms. 2024 Nov 29;12(12):2455. doi: 10.3390/microorganisms12122455.
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 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 . GA, differently from α-TOH, significantly reduced the -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 infection, which may help to treat inflammatory symptoms in VVC/RVVC.
外阴阴道念珠菌病（VVC）是一种常见的女性感染性疾病，其特征是阴道上皮出现过度炎症和损伤，复发性外阴阴道念珠菌病（RVVC）每年会导致超过三次症状发作，影响全球近8%的女性。目前的抗真菌治疗可缓解症状，但往往无法恢复粘膜组织的炎症稳态并预防复发。首次在暴露于感染的阴道上皮细胞中研究了具有免疫调节特性的α-生育酚（α-TOH）和维生素E代谢物没食子酸（GA），以评估它们对恢复细胞稳态重要的炎症信号参数的影响。为此，在预先用GA或α-TOH处理然后感染的A-431阴道上皮细胞中，研究了蛋白激酶MKK3/6、p38应激激酶（SAPK）和ERK1/2，以及c-Fos转录因子和IL-6、IL-1α和IL-1β的分泌。与α-TOH不同，GA显著降低了感染诱导的p38-SAPK激活，同时增加了促生存丝裂原活化蛋白激酶ERK1/2的活性。这导致炎症细胞因子IL-6、IL-1α以及IL-1β的分泌水平显著降低。总体而言，我们的数据表明，GA具有恢复暴露于感染的阴道上皮免疫代谢特性的潜力，这可能有助于治疗VVC/RVVC中的炎症症状。
