Crucial effect of interleukin-17/IL-17RC signaling on bio-functions of alveolar type II epithelial cell through Akt and STAT pathways

Abstract

Abstract The aim of this study was to explore the role of interleukin (IL)-17/IL-17RC signaling in the function of human alveolar type II epithelial cell-derived cell line of A549 cells. An in vitro LPS-challenged A549 cell model was established to assess the expression of IL-17RC. The effects of IL-17 alone or with LPS in A549 were evaluated by detecting the expression of surfactant protein A (SPA), epithelial sodium channel (ENaC), inflammatory cytokine tumor necrosis factor (TNF)-α and IL-8. Moreover, IL-17RC neutralizing antibody and STAT inhibitor were employed to explore the mechanism underlying IL-17/IL-17RC signaling influencing on A549 cell biological behavior. IL-17RC was expressed on A549 cells and showed a time and LPS dose dependent manner. IL-17 treatment could exert a synergistic effect with LPS, which could result in significantly elevated expression level of TNF-α and IL-8 and reduced expression level of SPA and ENaC. Activation of phosphorylation Akt and STAT were involved in the process of IL-17/IL-17RC signaling effects on A549 cell biological behavior and inhibition the Akt and STAT pathway with AG490 could reverse the effects exerted by IL-17/IL-17RC signaling. The results demonstrated that IL-17/IL-17RC signaling could modulate the biological function of human alveolar type II epithelial cell-derived A549 cells via promoting TNF-α and IL-8 expression, suppressing SPA and ENaC expression, and through activating Akt and STAT signaling pathway.