Astaxanthin prevents tuberculosis-associated inflammatory injury by inhibiting the Caspase4/11-Gasdermin-pyroptosis pathway

Abstract Introduction Pyroptosis, also known as inflammatory necrosis, is a programmed cell death caused by inflammation. Multiple studies suggest that Mycobacterium tuberculosis (MTB) infection causes tissue pyroptosis. However, there are currently no protective drugs against inflammatory damage caused by pyroptosis. In this study, the anti-pyroptotic effects of the natural compound Astaxanthin (ASTA) in a simulated pulmonary tuberculosis-associated inflammatory environment were explored. Methods In the established LPS-induced apoptosis co-culture system of MEL-12 cells and RAW246.7 macrophages，we detected the expression of key proteins Caspase4, Caspase11 and Gasdermin D in the pyroptosis pathway.Results The results showed that ASTA was able to maintain the stability of MLE-12 lung epithelial cell numbers in the inflammatory environment established by LPS. But the reason is not to promote cell proliferation, but to inhibit LPS-induced pyroptosis. The results showed that ASTA significantly inhibited the expression of key proteins in the Caspase4/11-Gasdermin D pathway and the release of pyroptosis-related inflammatory mediators. Conclusion Therefore, ASTA inhibits inflammation-induced pyroptosis by inhibiting the G pathway, and has the potential to protect lung tissue from tuberculosis-related inflammatory injury. ASTA, a functional food component, is a promising candidate for protection against tuberculosis-associated inflammatory lung injury.