α-MSH attenuates bleomycin-induced pulmonary fibrosis via NF-κB and inflammation suppression

Objective

Pulmonary fibrosis is a lung disease with high mortality and a lack of safe and effective treatments. α-MSH, a neuroimmunomodulatory peptide, has reported antifibrotic effects. This study aimed to study the mechanism by which α-MSH improves pulmonary fibrosis.

Methods

Macrophage and mouse pulmonary fibrosis models were established via bleomycin or LPS induction. In these models, inflammatory factor expression was detected via ELISA and qRT‒PCR, apoptosis levels were measured via flow cytometry, α-SMA and Collagen I expression were assessed via immunohistochemistry, and NF-κB activity was analyzed via Western blotting.

Results

LPS and bleomycin synergistically promoted macrophage secretion of TNF-α, IL-1β, IFN-γ, and IL-10, upregulated CD14 expression, and increased cell apoptosis, whereas α-MSH treatment (100 nmol/L for 24 h) significantly inhibited these effects. In the mouse pulmonary fibrosis model (bleomycin or/and LPS treatment), TNF-α, IL-1β, IFN-γ, and ELA2 levels were elevated in bronchoalveolar lavage fluid (BALF) and serum, while TNF-α, IL-1β, IFN-γ, IL-10, α-SMA, Collagen I, and NF-κB activity were upregulated in lung tissues. α-MSH treatment (50 μg/kg for 3 weeks) suppressed inflammatory factor secretion, reduced fibrosis-related factor expression, and decreased NF-κB activity.

Conclusion

α-MSH inhibits NF-κB activation and inflammation, thereby exerting antifibrotic effects. These findings support α-MSH as a promising therapeutic candidate for pulmonary fibrosis.