Serine protease inhibitor MDSPI16 ameliorates LPS-induced acute lung injury through its anti-inflammatory activity

Abstract A previous study described a novel serine protease inhibitor 16 from Musca domestica (MDSPI16), which inhibited the elastase and chymotrypsin. It also exhibited a potential anti-inflammatory activity for acute lung injury (ALI), while its effects on ALI are yet to be elucidated. The present study aimed to investigate the effects and the underlying mechanisms of MDSPI16 on lipopolysaccharide (LPS)-challenged mice and bone marrow neutrophils. The ALI model based on the results of LPS-induced mice demonstrated that MDSPI16 markedly reduced the infiltration of inflammatory cells, protein exudation in lung tissues, and downregulated the level of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α). Furthermore, the LPS-stimulated mouse bone marrow neutrophils model was employed to determine the role of MDSPI16. The cytokine levels were quantified by both the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Consequently, the expression of IL-6, IL-1β, and TNF-α was found to be inhibited by MDSPI16 in a dose-dependent manner. Moreover, MDSPI16 also inhibited the mouse neutrophils nuclear factor-κB (NF-κB) signaling pathway, c-Jun N-terminal kinase (JNK) signaling pathway, ERK1/2 and AP-1 signaling pathway in addition to the expression of iNOS and COX-2 proteins, which in turn, might alleviate the release of pro-inflammatory cytokines during ALI. Therefore, MDSPI16 could be proposed as a potential and novel drug therapy for ALI.