title: Perspective of cytokine regulation for periodontal treatment: fibroblast biology.
abstract: Efforts to understand the pathogenesis of periodontal diseases have been underway for decades. Studies of immunological aspects in addition to the structural components of gingival fibroblasts showed that the fibroblasts actively participate in immune and inflammatory events in periodontal diseases. Future strategies for the prevention and treatment of periodontal diseases should biologically regulate fibroblast activities. These cells are surrounded by monocyte-derived proinflammatory cytokines such as interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and lymphocyte-derived interleukin-6 (IL-6) in inflamed gingival tissue. Recent anti-cytokine therapy for inflammatory diseases including rheumatoid arthritis aimed to inhibit the binding of cytokines to targeted cells such as fibroblasts and condrocytes. IL-1beta and TNF-alpha are thought to be therapeutic targets because these cytokines are essential for the initiation of inflammatory immune reactions and are produced for prolonged periods in inflammatory diseases. IL-6 is also a target, because it is abundantly present in inflammatory lesions and activates fibroblasts in the presence of soluble IL-6 receptor. In addition, these cytokines accelerate gingival fibroblasts to produce collagenolytic enzymes, resulting in tissue destruction. Soluble receptors for IL-1beta and TNF-alpha are suggested to be candidates for therapeutic molecules, but soluble receptor for IL-6 is suggested to be a factor-stimulating fibroblast. This paper will review the utilization of soluble receptors specific to inflammatory cytokines which potentially stimulate fibroblasts to regulate biological events involved in the pathogenesis of periodontal diseases.
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Takashiba
authors.forename: Koji
authors.initials: K
authors.lastname: Naruishi
authors.forename: Yoji
authors.initials: Y
authors.lastname: Murayama
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001695:Biology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology*; D005881:Gingiva / Q000166:cytology / Q000276:immunology*; D005891:Gingivitis / Q000276:immunology / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D061965:Matrix Metalloproteinase Inhibitors; D010510:Periodontal Diseases / Q000628:therapy*; D010518:Periodontitis / Q000628:therapy; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D061965:Matrix Metalloproteinase Inhibitors; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha