Effect of proinflammatory cytokines on the expression and regulation of human beta-defensin 2 in human dental pulp cells

Abstract

INTRODUCTION: Although the expression of human beta-defensin-2 (hBD-2) in odontoblasts from human dental pulp (HDP) has been reported, the production of hBD-2 and its regulation remains poorly understood. The aim of this study was to investigate the effect of cytokines on the induction of hBD-2 and its signaling mechanisms in HDP cells.

METHODS: After stimulation with tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL-1 alpha), reverse-transcriptase polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay experiments were performed to evaluate the effects of these cytokines on the production of hBD-2.

RESULTS: TNF-alpha and IL-1 alpha synergistically increased hBD-2 messenger RNA levels, protein expression, and activity. The up-regulation of hBD-2 by cytokines was attenuated by pretreatment with inhibitors of PKC, JNK, p38, ERK MAPK, nuclear factor-kappaB, and adenosine monophosphate-activated protein kinase (AMPK).

CONCLUSION: These results suggest that TNF-alpha and IL-1 alpha up-regulate HBD-2 expression in HDP cells through the PKC, JNK MAPK, p38, ERK, NF-kappaB, and AMPK pathways. Thus, the induction of hBD-2 by proinflammatory cytokines might up-regulate the pulpal host immune defense system.