Increased Presence of Interleukin‐6 (IL‐6) and IL‐8 Secreting Fibroblast Subpopulations in Adult Periodontitis

• Published in: Journal of periodontology (1970) 1998-08, Vol.69 (8), p.899-910
• Main Authors: Dongari‐Bagtzoglou, Anna I., Ebersole, Jeffrey L.
• Format: Article
• Language: English
• Subjects: Adult; Aged; CD40; CD40 Antigens - analysis; Cell Lineage; Cells, Cultured; Chronic Disease; Connective Tissue - immunology; Connective Tissue - metabolism; Connective Tissue - pathology; cytokines; Dentistry; Dinoprostone - analysis; Dinoprostone - secretion; Fibroblasts; Fibroblasts - immunology; Fibroblasts - secretion; Fluorescent Antibody Technique, Indirect; Gingiva - immunology; Gingiva - metabolism; Gingiva - pathology; Humans; Inflammation Mediators - analysis; Interleukin-1 - analysis; Interleukin-1 - secretion; Interleukin-6 - analysis; Interleukin-6 - secretion; Interleukin-8 - analysis; Interleukin-8 - secretion; Middle Aged; Periodontitis - immunology; Periodontitis - metabolism; Periodontitis - pathology; periodontitis/pathogenesis; Phenotype; Vimentin - analysis
• ISSN: 0022-3492; 1943-3670
• DOI: 10.1902/jop.1998.69.8.899

Periodontitis is a chronic inflammation of the supporting structures of the dentition which constitutes one of the most common causes of adult tooth loss. While certain microorganisms have been associated with the onset of the disease process, the exact pathogenetic mechanisms underlying periodontal destruction are still poorly understood. We have tested the hypothesis that gingival fibroblasts from diseased sites contribute to pathogenesis by possessing a secretory phenotype characterized by an exuberant secretion of inflammatory mediators and cytokines. Of the cytokines and mediators tested, fibroblast IL‐1β and prostaglandin E2 (PGE2) secretion was not different between health and disease. However, we have shown that fibroblasts from periodontal lesions produce in vitro greater amounts of IL‐6 and IL‐8 constitutively than healthy controls. When fibroblasts were stimulated with a panel of endogenous or exogenous response modifiers, the magnitude of cytokine and mediator stimulation above constitutive levels did not differ between health and disease. A strong positive correlation was identified between IL‐6 or IL‐8 constitutive secretion levels in vitro and the in situ expression of these cytokines within the connective tissues from where these cells originated, indicating that the in vitro phenotype mirrors their in vivo function. Furthermore, we present evidence which indicates that increased cytokine secretion by fibroblasts in disease is due to an elevated proportion of subpopulations with higher cytokine secretory capacity. Finally, we demonstrated that cultures from diseased sites are composed of cells with higher levels of constitutive CD40 expression, which may contribute to the increased IL‐6 and IL‐8 secretory phenotype. J Periodontol 1998;69:899–910.