Procyanidin B2 alleviates LPS-induced acute lung injury by regulating M1 macrophage polarization and inhibiting pyroptosis via the NF-κB/JAK2/STAT1 signaling pathway

Acute lung injury (ALI) has attracted considerable attention because of its high mortality rate. Procyanidin B2 (PCB2) is widely present in various dietary foods and Plants. However, the effects of PCB2 on lung macrophages in LPS-induced ALI and the underlying molecular mechanisms have not yet been reported. The objective of the present study was to examine the effects of PCB2 on LPS-induced ALI and macrophages and the related mechanisms. Immunofluorescence, ELISA, qRT‒PCR, H&E staining and Western blotting were used for in vivo and in vitro experiments. The outcomes showed that PCB2 effectively alleviated ALI by reducing the lung wet‒dry (W/D) ratio, improving histopathological changes, decreasing the levels of IL-1β, TNF-α, IL-6 and reducing M1 polarization of lung macrophages. Both in vitro and in vivo, PCB2 inhibited the activation of the NF-κB and JAK2/STAT1 signaling pathways, suppressed the expression of Caspase-1, NLRP3, ASC proteins, and the expression of CD80, CD86, and iNOS, while increasing the expression of CD206. Our findings suggested that PCB2 inhibited the activation of the NF-κB and JAK2/STAT1 signaling pathways, thereby alleviating macrophage Pyroptosis and M1 polarization in LPS-caused ALI. PCB2 holds considerable promise as a potential therapeutic option for ALI.

Acute lung injury; JAK2/STAT1; Macrophage; NF-κB; Pyroptosis.