Aspergillus fumigatus-stimulated induction of IL-۳۳, IL-۲۵, IL-۱۳, TSLP and microRNAs is suppressed by propolis extract

Background: Aspergillus fumigatus (A. fumigatus) is an opportunistic fungus responsible for immunopathology, exacerbating asthma and changing the structure of the lung with chronic impacts on pulmonary function. There is a need to develop new medications for the treatment of allergic aspergillosis. The purposes of this study were to investigate the effect of propolis ethanolic extract on the release of IL-۳۳, IL-۲۵, IL-۱۳, and TSLP cytokines, the expression of miR-۲۱, miR-۱۵۵, and miR-۱۴۶a, and lung histopathology of mice sensitized by A. fumigatus conidia. Methods: Thirty-six Balb/c mice were divided into ۴ groups with ۹ animals including group A: mice received PBS (control); group B: mice sensitized by A. fumigatus conidia; group C: A. fumigatus-sensitized mice treated with propolis; group D: mice treated with propolis. After treatments, an ELISA was performed to measure the concentrations of the cytokines in the sera of the mice. QRT-PCR was performed to assess the expression levels of miR-۲۱, miR-۱۵۵, and miR-۱۴۶a genes. Ultimately, the mice were euthanized, and their lungs were separated for histopathological examination. Results: We found that A. fumigatus exposure rapidly induced the expression of ۴ key type ۲-promoting cytokines, IL-۳۳, IL-۲۵, IL-۱۳, and TSLP, in the sera of sensitized mice. A. fumigatus also induced the expression of miR-۱۵۵, miR-۱۴۶a, and miR-۲۱. Atelectasis, hyperemia of blood vessels, and hyperplasia of smooth muscles in pulmonary arterioles were observed in sensitized mice. In addition, propolis significantly reduced the release of IL-۳۳, IL-۲۵, and IL-۱۳ in sensitized mice sera (p<۰.۰۵), while TSLP amounts were not affected by propolis (p>۰.۰۵). We also showed that propolis significantly decreased the expression of miR-۲۱ which was elevated by A. fumigatus conidia (p<۰.۰۵). Conclusion: It was concluded that the direct effect of A. fumigatus on airway epithelial cells are likely to contribute to allergic airway diseases, and propolis directly decreased epithelial cell inflammatory responses to A. fumigatus

کلیدواژه ها:

Aspergillus fumigatus ، Allergic pulmonary aspergillosis ، IL-۳۳ ، TSLP ، miRs ، propolis