IL-22Up-regulates Beta-defensin-2Expression In Human Alveolar Epithelium Via STAT3but Not NF-κB Signaling Pathway

Objective: human beta-Defensin-2(HBD-2) is highly expressed by Th17cytokineinduction in the lung and exhibit broad-spectrum antimicrobial activity. Our studyinvestigates whether IL-22regulates HBD-2expression on human alveolar type IIepithelial cell lines A549and its mechanism invoved.Methods: flow cytometry(FCM) detected the expression of IL-22R on humanalveolar type II epithelial cell lines A549; Kinetics studies of IL-22effects onHBD-2mRNA by reverse transcriptase polymerase chain reaction(RT-PCR);RT-PCR and ELISA analyzed the effects of AG490and JSH-23, inhibitors ofp-STAT3DNA binding and NF-κB/p65subunit nuclear translocation respectively,on HBD-2by IL-22stimulated A549cells; Western Blotting detected STAT3phosphorylation and Immunofluorescence analyzed p-STAT3and NF-κBtranslocation of A549cells after IL-22treatment.Results: we observed that IL-22receptors high expressed on the membrane of A549cells; HBD-2mRNA was expressed in a time-and concentration-dependentmanners in human alveolar epithelial cell lines A549when treated with IL-22;Further studies demonstrated that HBD-2expression was attenuated by AG490, butto JSH-23.Conclusions: these results support that IL-22-mediated signaling pathway of HBD-2gene expression involved STAT3but not NF-κB in human alveolar epithelial celllines A549. These findings provide a new insight into how IL-22may play an important link between innate and adaptive immunity, thereby anti-infection locallyin the alveolar epithelium.