Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis
Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis
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DOI：
10.1172/jci118650
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发表时间：
1996-05-01
影响因子：
15.9
通讯作者：
Modlin, RL
中科院分区：
文献类型：
--
作者：
Uyemura, K;Demer, LL;Modlin, RL
已知T细胞细胞因子在确定感染性疾病的保护和病理学中起主要作用。最近已经清楚，IL-12是以产生IFN-γ为特征的1型T细胞细胞因子模式的关键诱导剂。相反，n-10下调IL-12产生和1型细胞因子应答。我们已经研究了IL-12和IL-10是否可能参与慢性炎症反应，动脉粥样硬化。在动脉粥样硬化斑块中，我们发现与正常动脉相比，IFN-γ mRNA的表达较强，但IL-4 mRNA的表达不强。IL-12 p40 mRNA和IL-12 p70蛋白在动脉粥样硬化斑块中也有表达。IL-12诱导单核细胞在体外响应于高度氧化的LDL，但没有最低限度的修饰LDL。IL-10在某些动脉粥样硬化病变中的表达表明了IL-10的交叉调节作用，并且证明外源性rIL-10抑制LDL诱导的IL-12释放。这些数据表明，IL-12和IL-10产生之间的平衡有助于动脉粥样硬化中免疫介导的组织损伤水平。
T cell cytokines are known to play a major role in determining protection and pathology in infectious disease. It has recently become clear that IL-12 is a key inducer of the type 1 T cell cytokine pattern characterized by production of IFN-gamma. Conversely, n-10 down-regulates IL-12 production and type 1 cytokine responses. We have investigated whether IL-12 and IL-10 might be involved in a chronic inflammatory reaction, atherosclerosis. In atherosclerotic plaques, we found strong expression of IFN-gamma but not IL-4 mRNAs as compared to normal arteries. IL-12 p40 mRNA and IL-12 p70 protein were also found to be abundant in atherosclerotic plaques. IL-12 was induced in monocytes in vitro in response to highly oxidized LDL but not minimally modified LDL. The cross-regulatory role of IL-10 was indicated by the expression of IL-10 in some atherosclerotic lesions, and the demonstration that exogenous rIL-10 inhibited LDL-induced IL-12 release. These data suggest that the balance between IL-12 and IL-10 production contributes to the level of immune-mediated tissue injury in atherosclerosis.