The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)-induced inflammation and ALI. We used corticosteroid treatment for LPS-induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo. Moreover, LPS-stimulated macrophages were used to explore the specific anti-inflammatory effects of corticosteroids on NLRP3-inflammasome in vitro. We found corticosteroids attenuated LPS-induced ALI, which manifested in reduction of the alveolar structure destruction, the infiltration of neutrophils and the inflammatory cytokines release of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in Lung. In vitro, when NLRP3-inflammasome was knocked out, inflammatory response of caspase-1 activation and IL-1β secretion was obviously declined. Further exploration, our results showed that when corticosteroid preprocessed macrophages before LPS primed, it obviously inhibited the activation of caspase-1 and the maturation of IL-1β, which depended on inhibiting the nuclear factor-κB (NF-κB) signal pathway activation. However, when corticosteroids intervened the LPS-primed macrophages, it also negatively regulated NLRP3-inflammasome activation through suppressing mitochondrial reactive oxygen species (mtROS) production. Our results revealed that corticosteroids played a protection role in LPS-induced inflammation and ALI by suppressing both NF-κB signal pathway and mtROS-dependent NLRP3 inflammasome activation.
Keywords: NLRP3-inflammasome; acute lung injury; corticosteroids; mitochondrial reactive oxygen species.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.