IL-1-induced receptor activator of NF-κB ligand in human periodontal ligament cells involves ERK-dependent PGE2 production
IL-1-induced receptor activator of NF-κB ligand in human periodontal ligament cells involves ERK-dependent PGE2 production
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DOI：
10.1016/j.bone.2004.09.011
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发表时间：
2005-02-01
期刊：
影响因子：
4.1
通讯作者：
Okabe, K
中科院分区：
文献类型：
--
作者：
Fukushima, H;Jimi, E;Okabe, K
牙周炎是一种牙齿支撑组织的炎症性疾病，是人类最常见的传染病之一。牙周病原体促进炎症细胞因子如白细胞介素-1 （IL-1）和前列腺素E-2 (PGE(2))，导致牙槽骨破坏。在本研究中，我们利用人牙周韧带（PDL）细胞和小鼠脾细胞共培养系统研究了il -1诱导破骨细胞发生的细胞和分子机制。IL-1 α诱导酒石酸盐抗性酸性磷酸酶阳性（TRAP）细胞形成以剂量依赖的方式。IL-1 α上调nf - κ B配体受体激活因子（RANKL），下调骨保护素（OPG） mRNA表达。在IL-1 α刺激后8小时，共培养物中加入细胞渗透性PKI（一种cAMP/PKA信号通路抑制剂）可抑制IL-1 α诱导的TRAP（+）细胞形成。IL-1 α诱导的TRAP细胞形成可被环氧化酶(COX)-2的选择性抑制剂NS398或细胞外信号调节激酶（ERK）的特异性抑制剂PD98059完全阻断。NS398和PD98059预处理也能抑制IL-1 α对PDL细胞中RANKL的上调和OPG表达的下调。IL-1 α激活ERK磷酸化，PD98059显著抑制IL-1 α诱导的PDL细胞COX2 mRNA表达和PGE(2)产生。相比之下，NEMO结合域（NBD）肽，nf - κ B信号的特异性抑制剂，不影响IL-1 α诱导的COX2， RANKL或OPG mRNA的表达。这些结果表明IL-1 α。通过erk依赖性PGE(2)在PDL细胞中产生，通过提高RANKL相对于OPG的表达水平刺激破骨细胞的形成。(c) 2004 Elsevier Inc.版权所有。
Periodontitis, an inflammatory disorder of the supporting tissue of teeth, is one of the most common infectious diseases in humans. Peridontal pathogens promote inflammatory cytokines such as interleukin-1 (IL-1) and prostaglandin E-2 (PGE(2)), resulting in alveolar bone destruction. In the present study, we examined the cellular and molecular mechanisms of IL-1-induced osteoclastogenesis using a coculture system of human periodontal ligament (PDL) cells and mouse spleen cells. IL-1 alpha induced tartrate-resistant acid phosphatase positive (TRAP.) cell formation in a dose-dependent manner. IL-1 alpha up-regulated receptor activator of NF-kappa B ligand (RANKL) and down-regulated osteoprotegerin (OPG) mRNA expression in PDL cells. The addition of cell-permeable PKI, an inhibitor of the cAMP/PKA signaling pathway, to the cocultures 8 h after the IL-1 alpha stimulation inhibited IL-1 alpha-induced TRAP(+) cell formation. IL-1 alpha-induced TRAP cell formation was completely blocked by either NS398, a selective inhibitor of cyclooxygenase (COX)-2, or PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK). Pretreatment with NS398 and PD98059 also inhibited both the up-regulation of RANKL and the down-regulation of OPG expression by IL-1 alpha in PDL cells. IL-1 alpha activated ERK phosphorylation and PD98059 greatly inhibited both COX2 mRNA expression and PGE(2) production induced by IL-1 alpha in PDL cells. In contrast, NEMO binding domain (NBD) peptide, a specific inhibitor of NF-kappa B signaling, did not affect COX2, RANKL, or OPG mRNA expression induced by IL-1 alpha. These results suggest that IL-1 alpha. stimulates osteoclast formation by increasing the expression level of RANKL versus OPG via ERK-dependent PGE(2) production in PDL cells. (c) 2004 Elsevier Inc. All rights reserved.