STAT6 attenuated murine acute lung injury through NLRP3/p38 MAPK/NF-kappaB signaling in macrophages
Abstract Signal transducer and activator of transcription 6 (STAT6) is an intracellular transcription factor, it remained unclear whether STAT6 affects murine acute lung injury (ALI) through modulation of macrophage subtypes and NLRP3/p38 MAPK/NF-kappaB signaling. We in this study, intratracheal treated wild-type (WT) and STAT6-/- mice with 5 mg/kg LPS. Lung tissues and bronchoalveolar lavage (BAL) were collected 2 days after the treatment. The results showed that lack of STAT6 in STAT6-/- mice caused more severe lung inflammation, neutrophil influx, and the expression of TNF-α, IL-6 and IL-1β in the inflamed lung tissues. Flow cytometry analysis showed Siglec F-CD206- biased polarization of M1 subtype macrophages in the LPS-treated STAT6-/- mice. In addition, lack of STAT6 increased the expression of NLRP3, p-p38 M APK, TNF-α, IL-1β and Calreticulin in the lung tissues of LPS-treated mice and STAT6-/- bone marrow-derived macrophages (BMDMs). However, Glibenclamide, PDTC and SB203580 effectively reversed the up-regulated pro-inflammatory cytokines in STAT6-/- BMDMs. Thereby, STAT6 defciency increased ALI severity, possibly through increasing polarization of M1 subtype macrophages and NLRP3/p38 MAPK/NF-kappaB signaling. NLRP3/p38 MAPK/NF-kappaB signaling may particiupate in the polarizatin of M1 subtype macrophages. Modulation of macrophages subtypes by molecular intervention of STAT6 signaling would be a promising therapeutic approach in the treatment of ALI.