Tumor necrosis factor-α (TNF-α)-induced and interleukin-1β (IL-1β)-induced shedding of TNF receptors from gingival fibroblasts
Tumor necrosis factor-α (TNF-α)-induced and interleukin-1β (IL-1β)-induced shedding of TNF receptors from gingival fibroblasts
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DOI：
10.1089/107999000750053744
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发表时间：
2000-12-01
影响因子：
2.3
通讯作者：
Murayama, Y
中科院分区：
文献类型：
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作者：
Ohe, H;Takashiba, S;Murayama, Y
肿瘤坏死因子-α（TNF-α）通过结合两种不同的受体（TNFR55和TNFR75）发挥其功能，TNFR55和TNFR75均以细胞相关和可溶形式存在。可溶性 TNF 受体 (sTNFR)、sTNFR55 和 sTNFR75 在炎症刺激下会蛋白水解脱落，然后调节各种 TNF-α 生物活性。由于人牙龈成纤维细胞 (HGF) 可能是发炎牙龈中 TNF-α 的潜在靶标，因此我们假设 HGF 通过调节自身的 TNFR 部分调节细胞对 TNF-α 的反应。在本研究中，体外研究了培养的 HGF 两种受体对促炎细胞因子 TNF-α 和白细胞介素 1 β (IL-1 β) 的反应的细胞相关形式和可溶形式的表达动力学。 TNF-α和IL-1β均上调TNFR75的基因表达，但不影响TNFR55的基因表达。 TNF-α 和 IL-1 β 降低 [I-125]TNF-α 与 HGF 的结合。此外，TNF-α和IL-1β上调HGF中sTNFR75的释放，但不上调sTNFR55的释放。这些结果表明炎症条件下的HGF可能通过优先诱导和脱落TNFR75而导致循环TNF-α的失活。
Tumor necrosis factor-alpha (TNF-alpha) exerts its functions by binding two different receptors (TNFR55 and TNFR75), Both TNFR55 and TNFR75 exist in cell-associated and soluble forms. Soluble TNF receptors (sTNFR), sTNFR55 and sTNFR75, are proteolytically shed upon inflammatory stimuli and then modulate various TNF-alpha bioactivities. As human gingival fibroblasts (HGF) can be potential targets for TNF-alpha in inflamed gingiva, we hypothesized that HGF partially modulate the cellular responses to TNF-alpha by regulating their own TNFR. In this study, the kinetics of expression of cell-associated and soluble forms of both receptors from cultured HGF in response to proinflammatory cytokines TNF-alpha and interleukin-1 beta (IL-1 beta) were investigated in vitro. Both TNF-alpha and IL-1 beta upregulated the gene expression of TNFR75 and did not affect that of TNFR55. TNF-alpha and IL-1 beta decreased binding of [I-125]TNF-alpha to HGF. Moreover, TNF-alpha and IL-1 beta upregulated the release of sTNFR75 from HGF but not that of sTNFR55, These results suggest that HGF under inflammatory conditions may contribute to the inactivation of circulating TNF-a through the preferential induction and shedding of TNFR75.