Interferon-γ induces secretory group IIA phospholipase A2 in human arterial smooth muscle cells -: Involvement of cell differentiation, STAT-3 activation, and modulation by other cytokines
Interferon-γ induces secretory group IIA phospholipase A2 in human arterial smooth muscle cells -: Involvement of cell differentiation, STAT-3 activation, and modulation by other cytokines
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DOI：
10.1074/jbc.m002783200
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发表时间：
2000-07-28
影响因子：
4.8
通讯作者：
Hurt-Camejo, E
中科院分区：
文献类型：
--
作者：
Peilot, H;Rosengren, B;Hurt-Camejo, E
分泌型非胰磷脂酶A（2）（sPLA（2）-IIA）表达增加可能是动脉粥样硬化炎症反应的一部分。然而，控制人血管细胞中sPLA（2）-IIA产生的因素尚不清楚。我们研究了培养的人动脉平滑肌细胞（HASMC）对sPLA（2）-IIA表达和分泌的调节。在非增殖条件下培养3-14天后诱导SPLA（2）-IIA。SPLA（2）-IIA与重钙调蛋白（一种细胞骨架蛋白）和p27（一种G（1）细胞周期蛋白抑制剂）共表达，这些蛋白质是分化细胞特有的。进一步与50-500单位/ml的干扰素（IFN）-γ孵育显著增加sPLA（2）-IIA mRNA和分泌。IFN-γ诱导的sPLA（2）-IIA在细胞培养基中具有活性，并与细胞膜蛋白聚糖相关。IFN-γ诱导的sPLA（2）-IIA表达被肿瘤坏死因子（TNF）-α和白细胞介素（n）-10拮抗，单独加入TNF-α诱导sPLA（2）-IIA分泌显著但短暂（4 h）增加。IL-10本身不影响sPLA（2）-IIA的表达和分泌。IFN-γ刺激的sPLA（2）-IIA转录涉及STAT-3蛋白。有趣的是，IL-6而不是IFN-γ上调HepG 2细胞中的sPLA（2）-IIA表达，因此IFN-γ应答对sPLA（2）-IIA的诱导似乎是细胞特异性的。总之，导致细胞分化的条件诱导HASMC中sPLA（2）-IIA表达，并且进一步暴露于IFN-γ可以上调sPLA（2）-IIA转录和分泌。这种IFN-γ刺激作用可以由其他细胞因子调节。
Increased expression of secretory non-pancreatic phospholipase A(2) (sPLA(2)-IIA) could be part of the inflammatory reaction in atherosclerosis. However, the factors controlling sPLA(2)-IIA production in human vascular cells are unknown. We investigated regulation of sPLA(2)-IIA expression and secretion by human arterial smooth muscle cells in culture (HASMC), SPLA(2)-IIA was induced after 3-14 days of culture in non-proliferating conditions. SPLA(2)-IIA was co-expressed with heavy caldesmon, a cytoskeleton protein, and p27, a G(1) cyclin inhibitor, proteins characteristically expressed by differentiated cells, Further incubation with 50-500 units/mi of interferon (IFN)-gamma significantly increased sPLA(2)-IIA mRNA and secretion. IFN-gamma-induced sPLA(2)-IIA was found to be active in cell media and associated with cell membrane proteoglycans. IFN-gamma induced sPLA(2)-IIA expression was antagonized by tumor necrosis factor (TNF)-alpha and interleukin (n)-10, TNF-alpha added individually induced a significant but transient (4 h) increase in sPLA(2)-IIA secretion. IL-10 by itself did not affect sPLA(2)-IIA expression and secretion. IFN-gamma-stimulated sPLA(2)-IIA transcription involved STAT-3 protein. Interestingly, IL-6 but not IFN-gamma up-regulated the sPLA(2)-IIA expression in HepG2 cells, thus sPLA(2)-IIA induction by IFN-gamma response appears to be cell specific. In summary, conditions leading to cell differentiation induced sPLA(2)-IIA expression in HASMC and further exposure to IFN-gamma can up-regulate sPLA(2)-IIA transcription and secretion. This IFN-gamma stimulatory effect can be modulated by other cytokines.