Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, South Korea.
J Endod. 2010 Jan;36(1):64-9. doi: 10.1016/j.joen.2009.09.022.
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.
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.
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).
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.
尽管已经有报道称人类牙髓（HDP）成牙本质细胞中表达人β防御素-2（hBD-2），但其 hBD-2 的产生及其调控仍知之甚少。本研究旨在探讨细胞因子对 HDP 细胞中 hBD-2 的诱导及其信号机制的影响。
用肿瘤坏死因子-α（TNF-α）和白介素 1α（IL-1α）刺激后，通过逆转录聚合酶链反应、Western blot 和酶联免疫吸附试验实验来评估这些细胞因子对 hBD-2 产生的影响。
TNF-α 和 IL-1α 协同增加 hBD-2 信使 RNA 水平、蛋白表达和活性。细胞因子对 hBD-2 的上调作用可被 PKC、JNK、p38、ERK MAPK、核因子-κB 和单磷酸腺苷激活蛋白激酶（AMPK）抑制剂预处理所减弱。
这些结果表明，TNF-α 和 IL-1α 通过 PKC、JNK MAPK、p38、ERK、NF-κB 和 AMPK 途径上调 HDP 细胞中 hBD-2 的表达。因此，促炎细胞因子诱导 hBD-2 的产生可能会增强牙髓宿主的免疫防御系统。
