Tumor necrosis factor-alpha induces cell type and tissue-specific expression of chemoattractant cytokines in vivo.
Tumor necrosis factor-alpha induces cell type and tissue-specific expression of chemoattractant cytokines in vivo.
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发表时间：
1993-03
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通讯作者：
Yoshihiro Ohmori;Lawrence Wyner;S. Narumi;D. Armstrong;M. H. Stoler;Thomas A. Hamilton
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作者：
Yoshihiro Ohmori;Lawrence Wyner;S. Narumi;D. Armstrong;M. H. Stoler;Thomas A. Hamilton
重组小鼠肿瘤坏死因子-α(TNF-α)对趋化细胞因子家族成员(JE、KC、IP-10)在体内具有强烈的全身刺激作用。这三个基因对肿瘤坏死因子-α的敏感性不同，其表达表现出不同的组织特异性。IP-10是诱导最强的信使RNA，在肝、肾和脾中可见，但在肺或皮肤中很少。乙脑表现出类似的模式，尽管表达的幅度明显较低。KC的表达仅见于经肿瘤坏死因子-α处理的小鼠的肝脏。IP-10表达的时间过程是快速和短暂的，并表现出很强的剂量依赖性。在静脉注射肿瘤坏死因子-α的小鼠中，信使RNA定位于脾间质，而不是粘附性巨噬细胞或非粘附性淋巴细胞。原位杂交发现INTERFORY在脾红髓表达最多，在白髓表达很少或不表达。在体外，肿瘤坏死因子-α能有效刺激成纤维细胞中趋化因子信使RNA的表达，但不能刺激炎性腹膜巨噬细胞表达趋化因子信使RNA。这些结果表明，肿瘤坏死因子-α可能是体内趋化因子基因表达的重要刺激因子，主要的细胞类型可能是基质成纤维细胞、微血管内皮细胞和/或锚定的单核巨噬细胞亚群。
Recombinant murine tumor necrosis factor-alpha (TNF-alpha) was shown to be a strong, systemic stimulus in vivo for members of the chemoattractant cytokine gene families (JE, KC, IP-10). The three genes showed differential sensitivity to TNF-alpha, and their expression demonstrated differential tissue specificity. IP-10 was the most strongly induced messenger RNA and was seen in the liver, kidney, and spleen but very poorly in the lung or skin. JE exhibited a similar pattern, though the magnitude of expression was markedly lower. KC expression was seen only in the liver of TNF-alpha-treated mice. The time course of expression for IP-10 was rapid and transient and showed strong dose dependence. In mice treated with TNF-alpha intravenously, messenger RNA was localized in the splenic stroma but not in adherent macrophages or nonadherent lymphocytes. In situ hybridization found the majority of intercrime expression in the splenic red pulp with little or no expression seen in the white pulp. In vitro, TNF-alpha was a potent stimulus of chemoattractant messenger RNA expression in fibroblasts but not in inflammatory peritoneal macrophages. These results indicate that TNF-alpha may be an important stimulus for chemoattractant cytokine gene expression in vivo, and the primary cell types responsible may be either stromal fibroblasts, microvascular endothelium, and/or a subset of anchored mononuclear phagocytes.