Cytokine-dependent synergistic regulation of interleukin-8 production from human gingival fibroblasts
The aim of this study was to analyze the effects of IL-IB, TNF-a, IFN-y, IL-6, and IL-8 on IL-8 production by human gingival fibroblasts (HGF), and if prostaglandin E2 (PGE2) also affects IL-8 production by human gingival fibroblasts. The researchers took cultured fibroblasts from attached gingiva of healthy volunteers and plated them into microtitier plates. Various doses of recombinant human (rh) IL-1B, rhTNF-a, IFN-y, rhIL-6 or rhIL-8 were analyzed for 8 or 24 hours. In some wells indomethacin of PGE2 was added. The results revealed that HGF, stimulated with either IL-1B or TNF-a, secreted IL-8 in a dose-dependent manner. When HGF was combined with IFN-y or IL-6, this did not induce significant amounts of IL-8. When the investigators combined the IL-1B and TNF, they synergistically enhanced the IL-8 secretion of HGF. IFN-y caused a significant decrease in IL-8 secretion from either IL-1B- or TNF-a-stimulated HGF. HGF produced a large amount of PGE2 after stimulation of IL-1B and TNF-a, but not IFN-y. The combination of IL-IB and TNF-a caused a synergistic effect in PGE2 production by HGF compared with IL-IB. IFN-y enhanced PGE2 production by TNF-a-stimulated HGF. This study demonstrates that cytokines such as IL-IB synergistically upregulate HGF for II-8 production and it indicates that IFN-y down-regulate these stimulatory effects at the transcriptional level. [M.C.R.]
Takigawa, M., S. Takashiba, F. Myokai,K.Takahashi, H. Arai, H. Kurihara, and Y. Murayama, J Periodont, 65:1002, 1994