Wang P-L, Ohura K
Department of Pharmacology, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan.
Crit Rev Oral Biol Med. 2002;13(2):132-42. doi: 10.1177/154411130201300204.
Periodontal disease is the major cause of adult tooth loss and is commonly characterized by a chronic inflammation caused by infection of oral bacteria. Porphyromonas gingivalis (P. gingivalis) is one of the suspected periodontopathic bacteria and is frequently isolated from the periodontal pockets of patients with chronic periodontal disease. The lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of periodontitis. Gingival fibroblasts, which are the major constituents of gingival connective tissue, may directly interact with bacteria and bacterial products, including LPS, in periodontitis lesions. It is suggested that gingival fibroblasts play an important role in the host responses to LPS in periodontal disease. P. gingivalis LPS enhances the production of inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) in gingival fibroblasts. However, the receptor that binds with P. gingivalis LPS on gingival fibroblasts remained unknown for many years. Recently, it was demonstrated that P. gingivalis LPS binds to gingival fibroblasts. It was also found that gingival fibroblasts express CD14, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88). P. gingivalis LPS treatment of gingival fibroblasts activates several intracellular proteins, including protein tyrosine kinases, and up-regulates the expression of monocyte chemoattractant protein-1 (MCP-1), extracellular signal-regulated kinase 1 (ERK1), and signal-regulated kinase 2 (ERK2), IL-1 receptor-associated kinase (IRAK), nuclear factor-kappaB (NF-kappaB), and activating protein-1 (AP-1). These results suggest that the binding of P. gingivalis LPS to CD14 and TLR4 on gingival fibroblasts activates various second-messenger systems. In this article, we review recent findings on the signaling pathways induced by the binding of P. gingivalis LPS to CD14 and Toll-like receptors (TLRs) in gingival fibroblasts.
牙周病是成人牙齿脱落的主要原因，其通常的特征是由口腔细菌感染引起的慢性炎症。牙龈卟啉单胞菌（P. gingivalis）是疑似牙周病致病细菌之一，经常从慢性牙周病患者的牙周袋中分离出来。牙龈卟啉单胞菌的脂多糖（LPS）是牙周炎发展的关键因素。牙龈成纤维细胞是牙龈结缔组织的主要成分，在牙周炎病变中可能直接与细菌及细菌产物（包括LPS）相互作用。有研究表明，牙龈成纤维细胞在宿主对牙周病中LPS的反应中起重要作用。牙龈卟啉单胞菌LPS可增强牙龈成纤维细胞中炎性细胞因子如白细胞介素（IL）-1、IL-6、IL-8和肿瘤坏死因子α（TNF-α）的产生。然而，多年来牙龈成纤维细胞上与牙龈卟啉单胞菌LPS结合的受体一直未知。最近，有研究证明牙龈卟啉单胞菌LPS可与牙龈成纤维细胞结合。还发现牙龈成纤维细胞表达CD14、Toll样受体4（TLR4）和髓样分化初级反应基因88（MyD88）。用牙龈卟啉单胞菌LPS处理牙龈成纤维细胞可激活多种细胞内蛋白，包括蛋白酪氨酸激酶，并上调单核细胞趋化蛋白-1（MCP-1）、细胞外信号调节激酶1（ERK1）和信号调节激酶2（ERK2）、IL-1受体相关激酶（IRAK）、核因子-κB（NF-κB）和活化蛋白-1（AP-1）的表达。这些结果表明牙龈卟啉单胞菌LPS与牙龈成纤维细胞上的CD14和TLR4结合可激活各种第二信使系统。在本文中，我们综述了牙龈卟啉单胞菌LPS与牙龈成纤维细胞上的CD14和Toll样受体（TLRs）结合所诱导的信号通路的最新研究结果。
