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Cytokine‐Dependent Synergistic Regulation of Interleukin‐8 Production From Human Gingival Fibroblasts
Author(s) -
Takigawa Masayuki,
Takashiba Shogo,
Myokai Fumio,
Takahashi Keiso,
Arai Hideo,
Kurihara Hidemi,
Murayama Yoji
Publication year - 1994
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.1994.65.11.1002
Subject(s) - cytokine , autocrine signalling , tumor necrosis factor alpha , interleukin 8 , interleukin , secretion , interleukin 6 , paracrine signalling , immunology , chemistry , biology , medicine , endocrinology , receptor
H uman gingival fibroblasts (HGF) may have an important role in the orchestration of immuno‐participant cells infiltrating the gingiva in response to continuously recurring bacterial infection. To examine the cytokine network regulating HGF‐derived interleukin (IL)‐8, a potent neutrophil chemotactic cytokine, we analyzed the effects of inflammatory cytokines alone and in combination on IL‐8 production by HGF. IL‐1β, tumor necrosis factor‐ α (TNF‐ α ), interferon‐ γ (IFN‐ γ ), IL‐6, and IL‐8 were used as stimulants. HGF secreted IL‐8 in a dose‐dependent manner after stimulation with either IL‐1 β or TNF‐ γ , but not with IFN‐ γ or IL‐6. Furthermore, IL‐8 itself did not affect IL‐8 mRNA accumulation in HGF in an autocrine manner. The combination of IL‐1β and TNF‐α synergistically enhanced the secretion of IL‐8, whereas IFN‐ γ suppressed IL‐8 secretion by IL‐1 β ‐ or TNF‐ α ‐stimulated HGF. These effects were also observed at each level of IL‐8 mRNA expression in HGF. IL‐8 secretion by cytokine‐stimulated HGF was not influenced by the inhibition of PGE 2 synthesis with indomethacin, indicating that endogenous PGE 2 was not involved in IL‐8 production by HGF. These results indicate that IL8 production by HGF is synergistically stimulated by specific cytokines, IL‐1 β and TNF‐ α , and suggest that these stimulatory effects are down‐regulated by IFN‐ γ at the transcriptional level through PGE 2 ‐independent pathways. Thus, neutrophil‐mediated processes in periodontal disease may be regulated in part by HGF in the cytokine network of immuno‐participant cells. J Periodontol 1994;65:1002–1007 .