DIFFERENTIAL REGULATION OF ASTROCYTE TNF-ALPHA EXPRESSION BY THE CYTOKINES TGF-BETA, IL-6 AND IL-10
DIFFERENTIAL REGULATION OF ASTROCYTE TNF-ALPHA EXPRESSION BY THE CYTOKINES TGF-BETA, IL-6 AND IL-10
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DOI：
10.1016/0736-5748(94)00061-7
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发表时间：
1995-06-01
影响因子：
1.8
通讯作者：
LAW, RM
中科院分区：
文献类型：
--
作者：
BENVENISTE, EN;TANG, LP;LAW, RM
在这项研究中，我们证明了转化生长因子- β (tgf - β)、白细胞介素-10 （IL-10）和白细胞介素-6 （IL-6）抑制肿瘤坏死因子- α的表达。单独用tgf - β处理星形胶质细胞对tnf - α表达没有影响，但tgf - β在蛋白和mRNA水平上抑制了tnf - α表达的诱导。相反，IL-10和IL-6均抑制星形胶质细胞tnf - α蛋白的表达，但对mRNA水平无影响。IL-6预处理星形胶质细胞12-24小时后，暴露于诱导刺激下，IL-6介导的抑制程度最大，而IL-10即使在与诱导刺激同时添加时也是有效的抑制剂。总的来说，这些数据表明tgf - β、IL-6和IL-10都能够抑制星形胶质细胞中tnf - α的表达，尽管这些免疫抑制细胞因子在不同水平的基因表达上起作用；即转录水平的tgf - β和翻译水平的IL-10/IL-6。这些结果表明，tgf - β、IL-6和IL-10是大脑炎症条件下星形胶质细胞产生细胞因子的重要调节因子，并有助于控制有害细胞因子如tnf - α的产生。
In this study, we demonstrate that transforming growth factor-beta (TGF-beta), interleukin-10 (IL-10) and interleukin-6 (IL-6) inhibit tumor necrosis factor-alpha expression by primary rat astrocytes. Treatment of astrocytes with TGF-beta alone had no effect on TNF-alpha expression, however, TGF-beta suppressed induction of TNF-alpha expression at both the protein and mRNA level. In contrast, IL-10 and IL-6 both inhibited TNF-alpha protein expression by astrocytes, but had no effect on mRNA levels. The extent of IL-6- mediated inhibition was greatest when astrocytes were pretreated with IL-6 for 12-24 hr, then exposed to the inducing stimuli, while IL-10 was an effective inhibitor even when added simultaneously with the inducing stimuli. Collectively, these data indicate that TGF-beta, IL-6 and IL-10 are all capable of inhibiting TNF-alpha expression by astrocytes, although these immunosuppressive cytokines act at different levels of gene expression; i.e. TGF-beta at the transcriptional level and IL-10/IL-6 at the translational level. These results indicate that TGF-beta, IL-6 and IL-10 are important regulators of cytokine production by astrocytes under inflammatory conditions in the brain, and can contribute to controlling the production of detrimental cytokines such as TNF-alpha.