CD45-induced tumor necrosis factor α production in monocytes is phosphatidylinositol 3-kinase-dependent and nuclear factor-κB-independent
CD45-induced tumor necrosis factor α production in monocytes is phosphatidylinositol 3-kinase-dependent and nuclear factor-κB-independent
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DOI：
10.1074/jbc.274.47.33455
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发表时间：
1999-11-19
影响因子：
4.8
通讯作者：
Brennan, FM
中科院分区：
文献类型：
--
作者：
Hayes, AL;Smith, C;Brennan, FM
促炎症细胞因子肿瘤坏死因子-α在类风湿关节炎的发病机制中起着关键作用。调控单核/巨噬细胞产生肿瘤坏死因子的机制尚不完全清楚，但被认为既涉及可溶性因子，也涉及细胞/细胞与其他类型细胞的接触。某些细胞表面受体CD45、CD44和CD58的结合可诱导单核细胞产生肿瘤坏死因子α。在本文中，我们进一步研究了细胞表面受体(特别是CD45)诱导单核细胞肿瘤坏死因子α的信号通路，并比较了共同/独特的信号通路与内毒素的作用。结果表明，CD45结扎或脂多糖刺激诱导的单核细胞肿瘤坏死因子α分别受磷脂酰肌醇3-激酶和核因子-kappaB的调节，但受p38丝裂原活化蛋白激酶的调节相似。这些结果表明，共同的和独特的信号通路都被不同的刺激用来诱导肿瘤坏死因子α。这些观察结果可能对抑制肿瘤坏死因子α在疾病中产生的方法有重大影响，因为细胞因子在疾病中具有致病作用。
The pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of rheumatoid arthritis. The mechanisms involved in regulating monocyte/macrophage TNF alpha production are not yet fully understood but are thought to involve both soluble factors and cell/cell contact with other cell types. Ligation of certain cell surface receptors, namely CD45, CD44, and CD58, can induce the production of TNF alpha in monocytes. In this paper, we investigate further the signaling pathways utilized by cell surface receptors (specifically CD45) to induce monocyte TNF alpha and compare the common/unique pathways involved with that of lipopolysaccharide. The results indicate that monocyte TNF alpha induced upon CD45 ligation or lipopolysaccharide stimulation is differentially modulated by phosphatidylinositol 3-kinase and nuclear factor-kappa B but similarly regulated by p38 mitogen-activated protein kinase. These results demonstrate that both common and unique signaling pathways are utilized by different stimuli for the induction of TNF alpha. These observations may have a major bearing on approaches to inhibiting TNF alpha production in disease where the cytokine has a pathogenic role.