Modulation of cytokine production by human mononuclear cells following impairment of Na,K-ATPase activity
Modulation of cytokine production by human mononuclear cells following impairment of Na,K-ATPase activity
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DOI：
10.1016/s0167-4889(96)00116-4
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发表时间：
1997-01-10
影响因子：
5.1
通讯作者：
Hall, ND
中科院分区：
文献类型：
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作者：
Foey, AD;Crawford, A;Hall, ND
细胞因子，包括TNF α和IL-1 β，是慢性炎症过程和组织损伤的核心，这是类风湿关节炎等疾病的特征。长期产生这些分子的机制尚不清楚。我们之前已经证明Na， k - atp酶（一种调节细胞内阳离子水平的关键酶）在类风湿单核细胞上的活性受损。用瓦巴因在正常单核细胞上模拟这种“缺陷”已被证明可以诱导TNF α，特别是IL-1 β的产生，而IL-6的合成则受到抑制。当单核细胞用钠离子载体莫能菌素处理时，细胞因子产生的类似模式也被注意到。诱导细胞因子的产生与相应mRNA的上调有关，尽管也观察到加工后的IL-1 β的分泌增强。这些细胞反应背后的机制似乎与细胞膜上的钠/钙交换有关。Na、k - atp酶活性受损可能促进类风湿关节炎患者促炎细胞因子的分泌。
Cytokines, including TNF alpha and IL-1 beta, are central to the chronic inflammatory process and tissue damage that characterises diseases such as rheumatoid arthritis. The mechanisms responsible for long-term generation of these molecules are poorly understood. We have previously demonstrated impaired activity of Na,K-ATPase, a key enzyme regulating intracellular cation levels, on rheumatoid mononuclear cells. Mimicking this 'defect' on normal mononuclear cells with ouabain has been shown to induce TNF alpha and, in particular, IL-1 beta production, whereas IL-6 synthesis was suppressed. A similar pattern of cytokine generation was noted when mononuclear cells were treated with the sodium ionophore, monensin. Induction of cytokine production was related to up-regulation of the appropriate mRNA, although enhanced secretion of processed IL-1 beta was also observed. The mechanism underlying these cellular responses appears to involve sodium/calcium exchange across the cell membrane. Impaired Na,K-ATPase activity might promote pro-inflammatory cytokine secretion in patients with rheumatoid arthritis.