Kobayashi M, Okada N, Okamatsu Y, Mugikura K, Nishihara T, Hanazawa S, Kitano S, Hasegawa K
Department of Periodontics, Showa University Dental School, Tokyo, Japan.
J Dent Res. 1999 Apr;78(4):840-9. doi: 10.1177/00220345990780040401.
Interleukin-1 (IL-1) may play a critical role in immune and inflammatory responses in inflamed gingiva, and it is synthesized by a wide variety of host cells. In this study, we examined the regulatory effects of various cytokines on bioactive membrane IL-1 and intracellular IL-1 alpha production in cultured human gingival fibroblasts (HGF). Recombinant human (rh) IL-1 beta stimulated membrane IL-1 activity, which was mainly attributed to IL-1 alpha. rhIL-1 beta and rh tumor necrosis factor (TNF)-alpha stimulated HGF to produce intracellular IL-1 alpha, whereas rh interleukin-6 (IL-6), rh interleukin-4 (IL-4), and rh interferon (IFN)-gamma did not do so. Intracellular IL-1 alpha production induced by rhIL-1 beta or rhTNF-alpha may be partially related to protein kinase C (PKC) activation, because rhIL-1 beta or rhTNF-alpha-induced intracellular IL-1 alpha production was stimulated by pre-treatment with 12-o-tetradecanoylphorbol 13-acetate (TPA), a PKC activator, but was suppressed by the pre-treatment with 1-(5-isoquinoline-sulfonyl) -2-methylpiperazine dihydrochloride (H-7), which is a PKC inhibitor. rhIL-4 inhibited rhIL-1 beta- or rhTNF-alpha-induced intracellular IL-1 alpha production, but rhIL-6 had no effect on this production. Pre-treatment with rh IFN-gamma remarkably enhanced intracellular IL-1 alpha production induced by subsequent treatment with rhIL-1 beta or rhTNF-alpha. Simultaneous treatment with rhIFN-gamma and rhIL-1 beta inhibited rhIL-1 beta-induced intracellular IL-1 alpha production, but co-treatment with rhIFN-gamma and rhTNF-alpha enhanced rhTNF-alpha-induced intracellular IL-1 alpha production. These results suggest that in inflamed gingiva, pro-inflammatory cytokines such as IL-1 beta and TNF-alpha may induce bioactive intracellular IL-1 alpha production in human gingival fibroblasts and that this production can be differentially modulated by T-cell-derived cytokines such as IFN-gamma or IL4.
白细胞介素-1（IL-1）可能在炎症牙龈的免疫和炎症反应中起关键作用，并且它由多种宿主细胞合成。在本研究中，我们检测了各种细胞因子对培养的人牙龈成纤维细胞（HGF）中生物活性膜IL-1和细胞内IL-1α产生的调节作用。重组人（rh）IL-1β刺激膜IL-1活性，这主要归因于IL-1α。rhIL-1β和rh肿瘤坏死因子（TNF）-α刺激HGF产生细胞内IL-1α，而rh白细胞介素-6（IL-6）、rh白细胞介素-4（IL-4）和rh干扰素（IFN）-γ则无此作用。rhIL-1β或rhTNF-α诱导的细胞内IL-1α产生可能部分与蛋白激酶C（PKC）激活有关，因为rhIL-1β或rhTNF-α诱导的细胞内IL-1α产生受到PKC激活剂12-O-十四烷酰佛波醇13-乙酸酯（TPA）预处理的刺激，但受到PKC抑制剂1-（5-异喹啉磺酰基）-2-甲基哌嗪二盐酸盐（H-7）预处理的抑制。rhIL-4抑制rhIL-1β或rhTNF-α诱导的细胞内IL-1α产生，但rhIL-6对此产生无影响。rhIFN-γ预处理显著增强了随后rhIL-1β或rhTNF-α处理诱导的细胞内IL-1α产生。rhIFN-γ与rhIL-1β同时处理抑制了rhIL-1β诱导的细胞内IL-1α产生，但rhIFN-γ与rhTNF-α共同处理增强了rhTNF-α诱导的细胞内IL-1α产生。这些结果表明，在炎症牙龈中，促炎细胞因子如IL-1β和TNF-α可能诱导人牙龈成纤维细胞产生具有生物活性的细胞内IL-1α，并且这种产生可受到T细胞衍生的细胞因子如IFN-γ或IL-4的差异调节。
