Caffeic acid attenuates tissue damage and inflammatory response in Klebsiella pneumonia by modulating AhR-Src-STAT3-IL-10 signaling pathway.

ABSTRACT

CA is a plant derivative with antibacterial and antiviral pharmacological effects, however, the therapeutic effect of CA on Klebsiella pneumonia and its mechanism study is still unclear. A rat KP model was established in vitro, a pneumonia cell model was established in vivo, the histopathological changes in the lungs were observed by HE staining after CA treatment, the expression of relevant inflammatory factors was detected by ELISA, the changes in the expression of proteins related to the AhR-Src-STAT3-IL-10 signaling pathway were detected by Western blot and immunofluorescence in the lungs, and the interactions between the proteins were verified by COIP relationship. The results showed that CA was able to attenuate the injury and inflammatory response of lung tissues, and molecular docking showed that there were binding sites between CA and AhR, and COIP demonstrated that AhR interacted with both STAT3 and Ser. In addition, CA was able to up-regulate the expression levels of pathway-related proteins of AhR, IL-10, p-Src, and p-STAT3, and AhR knockdown was able to reduce LPS-induced inflammatory responses and up-regulate pathway-related proteins, whereas CA treatment of AhR-knockdown-treated A549 cells did not show any statistically significant difference compared with the AhR knockdown group, demonstrating that CA exerts its pharmacological effects. These findings elucidated the mechanism of CA in the treatment of KP and demonstrated that CA is a potential therapeutic agent for KP.