The differential roles of Act-1 and NF-κB in the regulation of various IL-17A-induced genes in A549 cells (134.95)

Abstract

Abstract It has been shown that IL-17A is a potent inducer of human beta-defensin (HBD)-2 in airway epithelia through the Act1-dependent NF-kB transcriptional regulation. In our recent findings, the induction of HBD-2 is very robust in human primary airway epithelia and human bronchial epithelial-1 (HBE-1). In contrast, A549, an alveolar epithelial cell line, has a very weak IL-17A-stimulated HBD-2 gene expression. We found A549 cell has an impaired NF-kB activation specific to IL-17A cytokine, since other pro-inflammatory cytokines could stimulate significant NF-kB and HBD-2 gene expression. In addition, over-expression of Act-1 protein in HBE-1 can significantly induce HBD-2 promoter activity in the absence of IL-17A, while in A549, no HBD-2 induction was observed regardless of the presence of IL-17A. Interestingly, the IL-17A-stimulated genes that have been discovered so far are mostly dependent on Act-1 and NF-kB activation. However, we found the extent of the regulation by Act-1 and NF-kB varies between different genes. By use of siRNA knockdown, we found some IL-17A-induced genes are strictly regulated by Act1 but only partially by NF-kB. Therefore, IL-17A can stimulate certain gene expressions even under a deficient NF-kB activation in A549 cells. These findings suggested there might be some molecules in addition to NF-kB regulated by Act1 to stimulate IL-17A gene expression.