Dexamethasone suppresses interleukin-1β-induced human β-defensin 2mRNA expression: involvementof p38 MAPK, JNK, MKP-1, andNF-κβ transcriptional factor in A549 cells

Abstract

Human b-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Glucocorticoids, on the other hand, exert immunosuppressive and anti-inflammatory actions. We have previously reported that interleukin (IL)-1b induces HBD-2 mRNA expression through the activation of nuclear factor-kB (NF-kB) transcriptional factor, as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3- kinase/AKT in A549 cells. In this study, we further investigated whether dexamethasone (Dex) controls IL-1b-induced HBD-2 mRNA expression in A549 cells and the molecular mechanism associated with it. Dex suppressed IL-1b-induced HBD-2 mRNA expression, which is mediated by a glucocorticoid receptor, at the transcriptional level. Interestingly, Dex attenuated IL-1b-mediated activation of p38 MAPK and JNK, but not of AKT. Dex increased the expression of MAPK phosphatase (MKP)-1, which dephosphorylated p38 MAPK, but not JNK, by IL-1b. However, although Dex did not inhibit the nuclear translocation of p65 NF-kB in response to IL-1b, it profoundly inhibited NF-kB promoter- and HBD-2 promoter-driven luciferase activities. These results suggest that Dex acts to inhibit IL-1b-induced HBD-2mRNA expression through blockage of the nuclear transcriptional activation of p65 NF-kB as well as through inactivation of p38 MAPK and JNK. Specifically, Dex-induced MKP-1 expression is responsible for the inactivation of p38 MAPK, but not JNK, in response to IL-1b in A549 cells.