Effect of Proinflammatory Cytokines on the Expression and Regulation of Human Beta-Defensin 2 in Human Dental Pulp Cells

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 α (TNF-α) and interleukin 1α (IL-1α), 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-α and IL-1α 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-κB, and adenosine monophosphate-activated protein kinase (AMPK). Conclusion: These results suggest that TNF-α and IL-1α up-regulate HBD-2 expression in HDP cells through the PKC, JNK MAPK, p38, ERK, NF-κB, and AMPK pathways. Thus, the induction of hBD-2 by proinflammatory cytokines might up-regulate the pulpal host immune defense system.