Wang P L, Sato K, Oido M, Fujii T, Kowashi Y, Shinohara M, Ohura K, Tani H, Kuboki Y
Department of Pharmacology, Osaka Dental University, Hirakata, Japan.
Arch Oral Biol. 1998 Sep;43(9):687-94. doi: 10.1016/s0003-9969(98)00056-9.
The lipopolysaccharides (LPS) of Porphyromonas gingivalis are implicated in the initiation and development of periodontal diseases. However, the mechanisms underlying P. gingivalis LPS-mediated periodontal destruction are still unknown. Here, it was found that P. gingivalis LPS activates human gingival fibroblasts (HGF) to release interleukin 6 (IL-6) via CD14. Flow-cytometric analysis showed that HGFs bind to fluorescein-isothiocyanate (FITC)-labelled LPS, and express CD14 on their surfaces. The binding of FITC LPS was competitively suppressed by unlabelled synthetic lipid A as well as by LPS. LPS-induced IL-6 production was inhibited by anti-CD14 monoclonal antibody in a dose-dependent manner. The binding of FITC LPS to HGF was abrogated by anti-CD14 monoclonal antibody. Engagement of LPS initiated the protein tyrosine phosphorylation of several intracellular proteins including extracellular signal-regulated kinase (ERK) 1 and 2, and these events were suppressed by the anti-CD14 monoclonal. These results suggest that CD14 is a cell surface binding site for LPS and is involved in the LPS-mediated activation of HGF.
牙龈卟啉单胞菌的脂多糖（LPS）与牙周疾病的发生和发展有关。然而，牙龈卟啉单胞菌LPS介导牙周破坏的潜在机制仍不清楚。在此研究中，发现牙龈卟啉单胞菌LPS通过CD14激活人牙龈成纤维细胞（HGF）释放白细胞介素6（IL-6）。流式细胞术分析显示，HGF可结合异硫氰酸荧光素（FITC）标记的LPS，并在其表面表达CD14。未标记的合成脂质A以及LPS均可竞争性抑制FITC LPS的结合。抗CD14单克隆抗体可剂量依赖性抑制LPS诱导的IL-6产生。抗CD14单克隆抗体可消除FITC LPS与HGF的结合。LPS的结合引发了包括细胞外信号调节激酶（ERK）1和2在内的几种细胞内蛋白的蛋白酪氨酸磷酸化，而这些事件被抗CD14单克隆抗体所抑制。这些结果表明，CD14是LPS的细胞表面结合位点，并参与LPS介导的HGF激活。
