Mechanism of IL-6 alleviating acute lung injury through regulating JAK2/STAT3 signaling pathway
Objective To explore the mechanism by which IL-6 attenuates acute lung injury(ALI)by regulating janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods Human lung cancer cell line A549 cells were divided into blank control group(normally cultured),lipopolysaccharide(LPS)group(treated with LPS),LPS+IL-6 overexpression group(treated with LPS and transfected with IL-6 overexpression plasmid),LPS+IL-6 interference group(treated with LPS and transfected with IL-6 interference plasmid),and LPS+empty load group(treated with LPS and transfected with empty plasmid).Cell counting kit-8(CCK-8)assay was used to detect the cell proliferation rate.Rate of apoptosis and reactive oxygen species(ROS)content were measured by flow cytometry.The contents of malondialdehyde(MDA)and superoxide dismutase(SOD)were detected by the kit.The levels of inflammatory factors of TNF-α,IL-6 and IL-1 β were detected by ELISA.The gene expression levels of IL-6,JAK2 and STAT3 were detected by qRT-PCR.The protein expression levels of phosphorylated JAK2(p-JAK2)/JAK2,and phosphorylated STAT3(p-STAT3)/STAT3 were determined by Western blot assay.Results Compared to the blank control group,overexpression of IL-6 increased the apoptosis rates,the contents of ROS,MDA,TNF-α,IL-6,IL-1β,the gene expression levels of JAK2 and STAT3,and the protein expression levels of p-JAK2 and p-STAT3 in ALI cells induced by LPS,and decreased the proliferation rate and the content of SOD;while results of interfering with IL-6 were the opposite.Conclusion IL-6 can inhibit the activation of JAK2/STAT3 signaling pathway,and reduce oxidative stress and inflammatory reaction,and thus attenuates ALI.
IL-6Janus kinase 2/Signal transducer and activator of transcription 3Acute lung injuryOxidative stressInflammation