title: The inhibition of interferon-gamma-induced upregulation of HLA-DR expression on cultured human gingival fibroblasts by interleukin-1 beta or tumor necrosis factor-alpha.
abstract: The purpose of this study was to examine the effect of inflammatory cytokines on IFN-gamma-induced HLA-DR expression on cultured human gingival fibroblasts by flow cytometry. Natural human IFN-gamma, recombinant human interleukin-1 beta (rhIL-1 beta), and rh tumor necrosis factor-alpha (rhTNF-alpha) were used. IFN-gamma-induced upregulation of HLA-DR expression was inhibited by simultaneously adding rhIL-1 beta or rhTNF-alpha (65.9% and 31.4% inhibition, respectively). Both rhIL-1 beta and rhTNF-alpha induced endogenous prostaglandin E2 (PGE2) from gingival fibroblasts, while IFN-gamma did not. The inhibitory effect of rhIL-1 beta or rhTNF-alpha on IFN-gamma-induced upregulation of HLA-DR expression was partially abated in the presence of indomethacin (reductions of 65.9% and 41.7%, respectively). Both rhIL-1 beta- and rhTNF-alpha-induced endogenous PGE2 synthesis were completely inhibited by adding indomethacin (P < 0.001). The addition of exogenous PGE2 inhibited the IFN-gamma-induced HLA-DR expression (P < 0.001). These observations suggest that the MCH class II expression on human gingival fibroblasts are influenced by the cytokine network and indirectly by the cytokine-mediated fibroblast PGE2.
authors.affiliation: Department of Periodontology and Endodontology, Okayama University Dental School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: H
authors.initials: H
authors.lastname: Kurihara
authors.forename: Y
authors.initials: Y
authors.lastname: Murayama
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis*; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005881:Gingiva / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin