title: Focal adhesion kinase activation is required for TNF-α-induced production of matrix metalloproteinase-2 and proinflammatory cytokines in cultured human periodontal ligament fibroblasts.
abstract: Since focal adhesion kinase (FAK) was proposed as a mediator of the inflammatory response, we have investigated the role of this molecule in the release of inflammatory cytokines by cultured human periodontal ligament fibroblasts (HPDLFs), cells that are thought to be important in the patient's response to periodontal infection. Human periodontal ligament fibroblasts were stimulated by tumor necrosis factor alpha (TNF-α) and its effects on interleukin (IL)-6 and IL-8 release were measured by ELISA. Expression of matrix metalloproteinase 2 (MMP-2) protein was analysed by western blotting. The levels of IL6, IL8, and MMP2 mRNA were evaluated by real-time PCR. Tumor necrosis factor alpha dose-dependently induced the phosphorylation of FAK, whereas small interfering FAK (siFAK) inhibited TNF-α-induced FAK phosphorylation. Tumor necrosis factor alpha also stimulated the production of IL-6, IL-8, and MMP-2 in a dose-dependent manner. Knockdown of FAK significantly suppressed TNF-α-induced expression of IL6 and IL8 mRNA and release of IL-6 and IL-8 protein in HPDLFs. Similarly, MMP-2 down-regulation was significantly prevented by siFAK. Our results strongly suggest that knockdown of FAK can decrease the production of TNF-α-induced IL-6, IL-8, and MMP-2 in HPDLFs. These effects may help in understanding the mechanisms that control expression of inflammatory cytokines in the pathogenesis of periodontitis.
authors.affiliation: Department of Periodontology, School of Stomatology, Zhengzhou University, Zhengzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Periodontology, School of Stomatology, Zhengzhou University, Zhengzhou, China.
authors.forename: Ya-jing
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Periodontology, School of Stomatology, Zhengzhou University, Zhengzhou, China.
authors.forename: Liu-yun
authors.initials: LY
authors.lastname: Guo
authors.affiliation: Department of Periodontology, School of Stomatology, Zhengzhou University, Zhengzhou, China.
authors.forename: Guo-fang
authors.initials: GF
authors.lastname: Wang
authors.affiliation: Department of Periodontology, School of Stomatology, Zhengzhou University, Zhengzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Periodontology, School of Stomatology, Zhengzhou University, Zhengzhou, China.
authors.forename: Er-li
authors.initials: EL
authors.lastname: Yue
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D051417:Focal Adhesion Kinase 1 / Q000187:drug effects* / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis*; D016209:Interleukin-8 / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: focal adhesion kinase; human periodontal ligament fibroblasts; matrix metalloproteinase-2; proinflammatory cytokines