Chlorogenic acid reduces inflammation by inhibiting the elevated expression of KAT2A to ameliorate lipopolysaccharide-induced acute lung injury

Br J Pharmacol. 2023 Mar 13. doi: 10.1111/bph.16069. Online ahead of print.


Background and purpose: Respiratory diseases have become a global health problem and may lead to acute lung injury (ALI) in severe cases. ALI progression is associated with complex pathological changes; however, there are currently no effective therapeutic drugs. Excessive activation and recruitment of immunocytes in the lungs and the release of large amounts of cytokines are considered the primary causes of ALI, but the cellular mechanisms involved remain unknown. Therefore, new therapeutic strategies need to be developed to control the inflammatory response and prevent the further aggravation of ALI.

Experimental approach: Lipopolysaccharide was administered to mice via tail vein injection to establish an ALI model. Key genes regulating lung injury in mice were screened by RNA-seq, and their regulatory effects on inflammation and lung injury were assessed in in vivo and in vitro experiments.

Key results: The key regulatory gene KAT2A upregulated the expression of inflammatory cytokines and induced lung epithelial injury. Chlorogenic acid, a small natural molecule and KAT2A inhibitor, inhibited the inflammatory response and significantly improved the decreased respiratory function caused by lipopolysaccharide administration in mice by inhibiting the expression of KAT2A.

Conclusions and implications: Targeted inhibition of KAT2A suppressed the release of inflammatory cytokines and improved respiratory function in this murine model of ALI. Chlorogenic acid, a specific KAT2A-targeting inhibitor, was effective in treating ALI. In conclusion, our results provide a reference for the clinical treatment of ALI and contribute to the development of novel therapeutic drugs for lung injury.

Keywords: Acute lung injury; Chlorogenic acid; Inflammatory cytokine; KAT2A; Targeted inhibition.