Triptolide suppresses interleukin-1β-induced human B-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-κB in A549 cells

The immunosuppressive effect of triptolide has been associated with suppression of T-cell activation. However, the immunosuppressive effects of triptolide on innate immunity in the epithelial barrier remain to be elucidated. Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide and plays an important role in the innate immunity. We have previously demonstrated that IL-1 beta induced HBD-2 mRNA expression in A549 cells through activation of nuclear factor-kappa B (NF-kappa B) transcriptional factor as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase (PI3K). In this study, we investigated effects of triptolide on IL-1 beta-induced HBD-2 mRNA expression in A549 cells. Triptolide inhibited IL-1 beta-induced HBD-2 mRNA expression in a dose-dependent manner. Addition of triptolide did not suppress activation of p38 MAPK, INK, or PI3K in response to IL-1 beta. Triptolide inhibited IL-1 beta-induced MAPK phosphatase-1 expression at the transcriptional level and resulted in sustained phosphorylation of INK or p38 MAPK, explaining the little effect of triptolide on IL-1 beta-induced phosphorylation of these kinases. Although triptolide partially suppressed IL-1 beta-mediated degradation of I kappa B-alpha and nuclear translocation of p65 NF-kappa B, triptolide potently inhibited NF-kappa B promoter-driven luciferase activity in A549 cells. These results collectively suggest that the inhibitory effect of triptolide on IL-1 beta-induced HBD-2 mRNA expression in A549 cells seems to be at least in part mediated through nuclear inhibition of NF-kappa B transcriptional activity, but not inhibition of p38 MAPK, JNK, or PI3K. This inhibition may explain the ability of triptolide to diminish innate immune response.