Molecular biological study on the IL-8 production in inflamed gingiva

发炎牙龈中IL-8产生的分子生物学研究

基本信息

批准号：
06671912
负责人：
TAKASHIBA Shogo
金额：
$ 1.34万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

In the initial steps of an immune reaction or inflammation in the skin and mucosa, the following cytokine cascade was postulated to occur in response to inflammatory stimuli such as lipopolysaccharide (LPS) , 1) inflammatory stimuli induced production of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) , 2) proinflammatory cytokine IL-1 and TNF-alpha induced production of leukocyte chemotactic and activating peptide/IL-8. This postulation was examined in mouse skin and in dermal fibroblasts cultured from it. By in situ hybridization, expression of the IL-8 gene was detected in nearly all cultured dermal fibroblasts with or without treatment with human recombinant (hr) IL-1beta and/or hrTNF-alpha. Moreover, cultured dermal fibroblasts were found to express the IL-1beta gene even without treatment. These results suggest that expression of the IL-8 gene in dermal fibroblasts in vitro was induced by proinflammatory cytokines such as IL-1beta presumably functioning in autocrine fashion. However, expression of the IL-8 gene was not induced in dermal fibroblasts in vivo by injecting hrIL-1beta and/or hrTNF-alpha into mouse skin whereas keratiocytes and endothelial cells expressed the IL-8 gene in the skin ; as revealed by in situ hybridization. These results indicate that the process of the IL-8 gene expression elicited by IL-1beta and TNF-alpha in dermal fibroblasts in vitro is quite different from those in keratinocytes and endothelial cells in vivo. Dermal fibroblasts are likely to remain insensitive to IL-1beta and TNF-alpha in non-inflammatory tissues, but become sensitive to them with respect to induction of the IL-8 gene expression in vitro.

在皮肤和粘膜中免疫反应或炎症的最初步骤中，假定以下细胞因子级联反应是响应炎症刺激（例如脂多糖（LPS），1）炎症刺激诱导的白介素1（IL-1）（IL-1）和肿瘤坏死因子α（Tnf-lpha（Tnf-cy）的炎症刺激的产生，2） TNF-Alpha诱导白细胞趋化性和激活肽/IL-8的产生。在小鼠皮肤和从中培养的皮肤成纤维细胞中检查了这种假设。通过原位杂交，在几乎所有培养的皮肤成纤维细胞中都检测到IL-8基因的表达，并没有治疗人类重组（HR）IL-1Beta和/或HRTNF-Alpha。此外，发现培养的皮肤成纤维细胞即使未经治疗也表达了IL-1Beta基因。这些结果表明，促炎细胞因子（例如IL-1BETA）诱导IL-8基因在体外成纤维细胞中的表达，可能是以自分泌方式发挥作用的。然而，通过将HRIL-1BETA和/或HRTNF-ALPHA注射到小鼠皮肤中，在体内诱导了IL-8基因的表达，而角膜细胞和内皮细胞表达皮肤中的IL-8基因；如原位杂交所揭示的。这些结果表明，在体外，IL-1Beta和TNF-Alpha引起的IL-8基因表达的过程与体内的角质形成细胞和内皮细胞中的过程完全不同。皮肤成纤维细胞可能对非炎性组织中的IL-1Beta和TNF-Alpha不敏感，但对于在体外诱导IL-8基因表达的诱导时，它们对它们变得敏感。