Ozaki K, Hanazawa S, Takeshita A, Chen Y, Watanabe A, Nishida K, Miyata Y, Kitano S
Department of Oral Microbiology, Meikai University School of Dentistry, Saitama, Japan.
Oral Microbiol Immunol. 1996 Apr;11(2):109-14. doi: 10.1111/j.1399-302x.1996.tb00344.x.
The present study demonstrates that interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) induce and synergistically stimulate monocyte chemoattractant protein-1 (MCP-1) expression in fibroblasts from human periodontal ligament. IL-1 beta and TNF-alpha induced in a dose-dependent manner the expression of the MCP-1 gene in the fibroblasts from the human periodontal ligament. However, such an inducing effect was not observed with IL-6 and interferon-gamma. The peak expression of the MCP-1 gene by IL-1 beta or TNF-alpha was observed at 3 h after initiation of their treatment. Furthermore, IL-1 beta in combination with TNF-alpha synergistically stimulated the MCP-1 gene expression in the cells. We also observed significant chemotactic activity for human monocytes in conditioned medium of fibroblasts from the human periodontal ligament treated with both cytokines. The stimulated chemotactic activity induced by these cytokines depended on both dose and treatment time. The chemotactic activity in conditioned medium of IL-1 beta-treated fibroblasts from the human periodontal ligament was neutralized by antiserum specific for MCP-1 protein. The MCP-1 gene product in conditioned medium of IL-1 beta-treated fibroblasts from the human periodontal ligament was shown to have a molecular mass of 11,000 Da by immunoprecipitation with the specific antiserum, and IL-1 beta also stimulated synergistically MCP-1 protein expression in combination with TNF-alpha. These results suggest that IL-1 beta and TNF-alpha may contribute to the infiltration of monocytes into inflammatory sites of periodontal ligament tissues via the MCP-1 gene product produced by fibroblasts from the human periodontal ligament.
本研究表明，白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）可诱导并协同刺激人牙周膜成纤维细胞中单核细胞趋化蛋白-1（MCP-1）的表达。IL-1β和TNF-α以剂量依赖性方式诱导人牙周膜成纤维细胞中MCP-1基因的表达。然而，IL-6和干扰素-γ未观察到这种诱导作用。IL-1β或TNF-α处理后3小时观察到MCP-1基因的峰值表达。此外，IL-1β与TNF-α联合可协同刺激细胞中MCP-1基因的表达。我们还观察到，在用这两种细胞因子处理的人牙周膜成纤维细胞的条件培养基中，对人单核细胞具有显著的趋化活性。这些细胞因子诱导的趋化活性取决于剂量和处理时间。人牙周膜IL-1β处理的成纤维细胞条件培养基中的趋化活性被MCP-1蛋白特异性抗血清中和。用人牙周膜IL-1β处理的成纤维细胞条件培养基中的MCP-1基因产物经特异性抗血清免疫沉淀显示分子量为11,000 Da，并且IL-1β与TNF-α联合也协同刺激MCP-1蛋白的表达。这些结果表明，IL-1β和TNF-α可能通过人牙周膜成纤维细胞产生的MCP-1基因产物促进单核细胞浸润到牙周膜组织的炎症部位。
