IL-10 inhibits Porphyromonas gingivalis LPS-stimulated human gingival fibroblasts production of IL-6. |
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Authors: | P L Wang S Shirasu M Shinohar Y Azuma M Daito H Yasuda K Ohura |
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Institution: | Department of Pharmacology, Department of Pediatric Dentistry, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, 573-1121, Japan. wang@cc.osaka-dent.ac.jp |
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Abstract: | Lipopolysaccharides (LPS) of Porphyromonas gingivalis have been implicated in the initiation and development of periodontal diseases. In a previous study, we investigated the signal transduction pathway of P. gingivalis and demonstrated that LPS stimulates the production of interleukin (IL)-6 in human gingival fibroblasts (HGFs), which in turn activates osteoclasts in vitro. The cytokine, IL-10, was initially described as cytokine synthesis inhibitory factor. In this study, we examined that effect of IL-10 on P. gingivalis LPS-induced human gingival fibroblast production of IL-6. LPS-induced IL-6 production was inhibited by IL-10 in a dose-dependent manner. Flow cytometric analysis showed that HGFs bind to fluorescein-isothiocyanate (FITC) labeled IL-10. Western blotting analysis demonstrated the expression of IL-10 receptor on the cell surface of these cells. Engagement of LPS initiated the protein tyrosine phosphorylation of several intracellular proteins including extracellular signal-regulated kinase 2 (ERK2), and these events were suppressed by IL-10. These results suggest that IL-10 inhibits the inflammatory response via the IL-10 receptor in P. gingivalis LPS-initiated periodontal diseases. |
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