Exploration of ω-9MUFAs: mitigating effect on lipopolysaccharide-induced acute lung injury.

Abstract

Given the demonstrated mitigating effect of omega-9 monounsaturated fatty acids (ω-9MUFAs) on lipopolysaccharide (LPS)-induced acute lung injury (ALI), we deeply explored corresponding mechanisms. Sprague-Dawley rats experienced ALI modeling, and received ω-9 MUFAs (3 mg/kg) injection via the tail vein. Post incubation in 100 ng/mL phorbol-12-myristate-13-acetate and 100 ng/mL LPS for 24 h each, THP-1 macrophages were transfected with shHSPH1 and c-MYC overexpression plasmid. Lung injury detection depended on H&E staining. Levels of inflammation-related factors were detected by ELISA. Levels of inflammation-related factors, heat shock protein family H (Hsp110) member 1 (HSPH1), c-MYC, stimulator of interferon response CGAMP interactor 1 (STING) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were measured by qRT-PCR. Levels of pyroptosis-related factors, HSPH1, c-MYC, STING, NLRP3, and M1 macrophage biomarkers were assayed by Western blot. Proportion of M1 macrophages and pyroptosis were detected by flow cytometry. Localization of HSPH1 and CD68 was measured by immunofluorescence assay. ω-9MUFAs reduced the inflammation, the proportion of M1 and pyroptotic macrophages and levels of HSPH1, c-MYC, STING and NLRP3 in ALI rats. The expression positions of HSPH1 and CD68 were overlapped in ALI rat lung tissue. HSPH1 silencing reversed the changes in inflammation, the proportion of M1 and pyroptotic macrophages and levels of c-MYC, STING and NLRP3 in LPS-induced THP-1 macrophages, and c-MYC overexpression offset these effects of HSPH1 silencing. Collectively, ω-9MUFAs ameliorated LPS-induced ALI by regulating HSPH1/c-MYC expression, down-regulating M1 macrophage polarization and pyroptosis.