J Korean Acad Periodontol.  1999 Dec;29(4):803-820. 10.5051/jkape.1999.29.4.803.

Effects of Direct Cell Contact Between Monocytes and Fibroblasts on the Interleukin-6 Production and Cell Proliferation of Human Gingival and Periodontal Ligament Fibroblasts

• Kim SA
• Lee H
• Oh KO
• Kim HS

• KMID: 1711936
• DOI: http://doi.org/10.5051/jkape.1999.29.4.803

Abstract

In order to reveal immunopathogenesis of periodontal tissue destruction, it is important to clarify the molecular mechanism of trafficking and retention of activated leukocytes, including monocytes/macrophages. Gingival fibroblasts may be involved in the regulation of inflammatory cell accumulation in the extravascular periodontal connective tissues via cytokine production and surface expression of adhesion molecules. In this study, it was investigated the molecular basis for the adhesive interactions between monocytes and fibroblasts such as periodontal ligament fibroblast(PDLF), human gingival fibroblast(HGF), and human dermal fibroblast(HDF). First, it was examined the evidence whether monocyte-fibroblast cell contact may cause signal transduction in fibroblasts. Being directly in contact with fixed human monocyte cell line THP-1, or U937, upregulation of IL-6 production, TNF-alpha mRNA expression and increased cell proliferation could be seen for fibroblasts. IL-6 production induced by monocyte-fibroblast coculture were further increased when fibroblasts had been pretreated with IFN-gamma or IL-1beta, and monocytes with LPS. Next, it was examined the expression of ICAM-1 which has been known to be involved in accumulation and activation of leukocytes in inflammatory diseases such as periodontitis. ICAM-1 was upregulated up to 10-fold on PDLF, HGF, and HDF by exposure to IFN-gamma or IL-1beta. Furthermore, anti-ICAM-1 monoclonal antibody clearly blocked coculture-induced IL-6 production by fibroblasts, suggesting that ICAM-1/beta2 integrin pathway is involved in periodontal fibroblast-monocyte interaction. Overall, these findings provide evidence that periodontal fibroblasts could be involved in the accumulation and retention of monocytes/macrophages in periodontal inflammatory lesion at least in part by ICAM-1 expression. In addition, periodontal fibroblast-monocyte interaction could cause activation signals in fibroblasts intracellularly which result in cytokine production and cell proliferation. Thus, periodontal fibroblasts are speculated to play an important role in immunoregulation and tissue destruction in chronic periodontal diseases by interaction with monocytes/macrophages.

MeSH Terms

Humans
Tumor Necrosis Factor-alpha