Modulation of cytokine production by human mononuclear cells following impairment of Na,K-ATPase activity

被引:26
作者
Foey, AD
Crawford, A
Hall, ND
机构
[1] UNIV BATH, BATH INST RHEUMAT DIS, SCH PHARM & PHARMACOL, BATH BA2 7AY, AVON, ENGLAND
[2] KNOLL PHARMACEUT, NOTTINGHAM, ENGLAND
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 1997年 / 1355卷 / 01期
基金
英国生物技术与生命科学研究理事会;
关键词
ATPase; Na+/K+-; mononuclear cell; cytokine; (human);
D O I
10.1016/S0167-4889(96)00116-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:43 / 49
页数:7
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