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首页> 外文期刊>Biochemistry >Arachidonic Acid-Induced IL-6 Expression Is Mediated by PKC alpha Activation in Osteoblastic Cells.
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Arachidonic Acid-Induced IL-6 Expression Is Mediated by PKC alpha Activation in Osteoblastic Cells.

机译:花生四烯酸诱导的IL-6表达是由成骨细胞中的PKCα激活介导的。

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摘要

There are several pieces of evidence supporting the important role that essential fatty acids (EFAs) and their metabolites play in regulating calcium and bone metabolism, and their relevance to the pathobiology of bone disease, with particular reference to modulating effects on cytokines. We found that arachidonic acid (AA) triggers a cell signal in osteoblasts and leads to the expression of IL-6. To explore the biochemical pathways involved in AA induction of cytokine gene expression, we evaluated the potential protein kinase C (PKC) dependent mechanism accounting for the AA effect on IL-6 gene expression. The osteoblast-like cell line MG-63 was pretreated with calphostin C, a PKC inhibitor, or phorbol 12-myristate 13-acetate (PMA) for an extended period, a condition which causes PKC downregulation, and subsequently with AA. After these treatments, IL-6 gene expression was no longer evident. We also showed that PKC and, in particular, PKC alpha, which are both recruited to the particulate fraction, undergo proteolysis and autophosphorylation; all of these steps are required for PKC activation and, subsequently, for AA-induced signaling. It is interesting that other unsaturated fatty acids, such as oleic acid (OA) or eicosapentaenoic acid (EPA), are unable to induce either PKC activation or IL-6 gene expression.
机译:有几项证据支持必需脂肪酸(EFA)及其代谢产物在调节钙和骨代谢中的重要作用,以及它们与骨骼疾病的病理生物学相关性,特别是对细胞因子的调节作用。我们发现花生四烯酸(AA)在成骨细胞中触发细胞信号并导致IL-6的表达。为了探索涉及AA诱导细胞因子基因表达的生化途径,我们评估了潜在的蛋白激酶C(PKC)依赖性机制,解释了AA对IL-6基因表达的影响。成骨细胞样细胞系MG-63用钙磷蛋白C,PKC抑制剂或佛波12-肉豆蔻酸酯13-乙酸酯(PMA)预处理了很长一段时间,这种情况会导致PKC下调,然后再用AA预处理。经过这些处理后,IL-6基因的表达不再明显。我们还表明,都被募集到颗粒级分的PKC,尤其是PKCα,会发生蛋白水解和自磷酸化。所有这些步骤对于PKC激活以及随后的AA诱导信号传导都是必需的。有趣的是,其他不饱和脂肪酸,例如油酸(OA)或二十碳五烯酸(EPA),既不能诱导PKC活化也不能诱导IL-6基因表达。

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