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

Area of Science:

• Biochemistry and Molecular Biology
• Immunology
• Pharmacology

Background:

• A novel serine protease inhibitor, MDSPI16 from Musca domestica, was previously identified.
• MDSPI16 demonstrated inhibitory effects on elastase and chymotrypsin, with potential anti-inflammatory activity.
• The specific therapeutic effects of MDSPI16 on acute lung injury (ALI) remained to be elucidated.

Purpose of the Study:

• To investigate the therapeutic effects of MDSPI16 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.
• To elucidate the underlying molecular mechanisms of MDSPI16's action in LPS-challenged mice and bone marrow neutrophils.

Main Methods:

• Established an ALI mouse model using LPS challenge.
• Quantified inflammatory cell infiltration and protein exudation in lung tissues.
• Measured cytokine levels (IL-6, IL-1β, TNF-α) using ELISA and qRT-PCR in vivo and in vitro.
• Assessed the impact of MDSPI16 on neutrophil signaling pathways (NF-κB, JNK, ERK1/2, AP-1) and protein expression (iNOS, COX-2).

Main Results:

• MDSPI16 significantly reduced inflammatory cell infiltration and protein exudation in LPS-induced ALI mice.
• MDSPI16 dose-dependently downregulated pro-inflammatory cytokine levels (IL-6, IL-1β, TNF-α) in lung tissues and neutrophils.
• MDSPI16 inhibited key inflammatory signaling pathways (NF-κB, JNK, ERK1/2, AP-1) and suppressed iNOS and COX-2 expression in neutrophils.

Conclusions:

• MDSPI16 demonstrates significant anti-inflammatory effects in an LPS-induced ALI mouse model.
• MDSPI16 alleviates ALI by inhibiting inflammatory cell infiltration, pro-inflammatory cytokine release, and key signaling pathways.
• MDSPI16 presents potential as a novel therapeutic agent for treating acute lung injury.