Cytokine-dependent synergistic regulation of interleukin-8 production from human gingival fibroblasts.
Human 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-1 beta, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, and IL-8 were used as stimulants. HGF secreted IL-8 in a dose-dependent manner after stimulation with either IL-1 beta or TNF-alpha, but not with IFN-gamma or IL-6. Furthermore, IL-8 itself did not affect IL-8 mRNA accumulation in HGF in an autocrine manner. The combination of IL-1 beta and TNF-alpha synergistically enhanced the secretion of IL-8, whereas IFN-gamma suppressed IL-8 secretion by IL-1 beta- or TNF-alpha-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 PGE2 synthesis with indomethacin, indicating that endogenous PGE2 was not involved in IL-8 production by HGF. These results indicate that IL-8 production by HGF is synergistically stimulated by specific cytokines, IL-1 beta and TNF-alpha, and suggest that these stimulatory effects are down-regulated by IFN-gamma at the transcriptional level through PGE2-independent pathways. Thus, neutrophil-mediated processes in periodontal disease may be regulated in part by HGF in the cytokine network of immuno-participant cells.
Department of Periodontology and Endodontology, Okayama University Dental School, Japan.
M
M
Takigawa
S
S
Takashiba
F
F
Myokai
K
K
Takahashi
H
H
Arai
H
H
Kurihara
Y
Y
Murayama
D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000276:immunology*; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005891:Gingivitis / Q000276:immunology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin