Differential regulation of lipoprotein lipase in the macrophage J774.2 cell line by cytokines
Differential regulation of lipoprotein lipase in the macrophage J774.2 cell line by cytokines
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DOI：
10.1006/cyto.1996.0071
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发表时间：
1996-07-01
期刊：
影响因子：
3.8
通讯作者：
Ramji, DP
中科院分区：
文献类型：
--
作者：
TengkuMuhammad, TS;Hughes, TR;Ramji, DP
细胞因子对巨噬细胞脂蛋白脂肪酶（LPL）的调节在动脉粥样硬化的发病机制和对内毒素挑战的反应中具有潜在的关键作用。然而，不同细胞因子调节巨噬细胞LPL活性表达的确切机制尚不清楚。因此，我们以小鼠J774.2细胞系为模型系统，研究了六种细胞因子和细菌脂多糖（LPS）对LPL功能的作用。尽管暴露于LPS、白细胞介素11 （IL-11）、肿瘤坏死因子α (tnf - α)、干扰素γ (ifn - γ)和IL-1，在生理浓度范围内，导致肝素释放的LPL活性、LPL mrna水平和LPL蛋白含量下降，但IL-6和白血病抑制因子（LIF）的刺激没有影响。ifn - γ对细胞LPL活性和mRNA水平的最大抑制作用（60%）低于LPS、IL-11、tnf - α和IL-1（78-97%）。每种细胞因子在抑制LPL活性和mRNA水平方面表现出典型的剂量依赖模式，其中il -11- tnf - α比ifn - γ /IL-1更有效。在所有剂量的IL-11、tnf - α、ifn - γ和IL-1下，LPL活性下降的80%以上是由于mRNA水平的相应降低。对LPS、IL-11、tnf - α、ifn - γ和IL-1的反应时间过程相似，每种情况下达到LPL活性一半最大抑制所需的时间在7到9.5小时之间。这些结果表明，J774.2巨噬细胞中的LPL受各种细胞因子的差异调节，IL-11、tnf - α、ifn - γ和IL-1降低LPL活性的主要控制因素是mRNA代谢水平（转录降低或RNA稳定性降低）。所确定的反应也显示出与先前描述的脂肪细胞（例如3T3-L1细胞系）的一些差异，从而表明存在细胞因子调节LPL的潜在细胞特异性机制。(C) 1996学术出版社有限公司
The regulation of macrophage lipoprotein lipase (LPL) by cytokines is of potentially crucial importance in the pathogenesis of atherosclerosis and in the responses to endotoxin challenge. However, the precise mechanisms by which different cytokines modulate the expression of macrophage LPL activity are poorly understood. The action of six cytokines and bacterial lipopolysaccharide (LPS) on LPL function using the murine J774.2 cell line as a model system has, therefore, been studied. Although exposure to LPS, interleukin 11 (IL-11), tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and IL-1, over the physiological range of concentrations, resulted in a decrease in the heparin-releasable LPL activity, LPL-mRNA levels and LPL-protein content of the cells, stimulation with IL-6 and leukaemia inhibitory factor (LIF) had no effect. The maximum suppression of LPL activity and mRNA levels in the cells by IFN-gamma (60%) was lower than that produced by LPS, IL-11, TNF-alpha and IL-1 (78-97%). Each cytokine displayed a characteristic dose-dependent pattern for the suppression of LPL activity and mRNA levels with IL-11-TNF-alpha being more potent than IFN-gamma/IL-1. More than 80% of the decrease in the LPL activity, at all doses of IL-11, TNF-alpha, IFN-gamma and IL-1, was due to a corresponding reduction in the mRNA levels. The time course of responses to LPS, IL-11, TNF-alpha, IFN-gamma and IL-1 were similar, with the time required to achieve half maximal suppression of LPL activity being between 7 and 9.5 h in each case. These results indicate that LPL in J774.2 macrophages is regulated differentially by various cytokines and that the major control responsible for the reduction of LPL activity by IL-11, TNF-alpha, IFN-gamma and IL-1 is exerted at the level of mRNA metabolism (decreased transcription or RNA stability). The responses identified also displayed several differences to those described previously for adipocytes (e.g. 3T3-L1 cell line), thereby suggesting the existence of potential cell-specific mechanisms for the regulation of LPL by cytokines. (C) 1996 Academic Press Limited