Bleich D, Chen S, Wen Y, Nadler J L
Division of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, California 91010, USA.
Biochem Biophys Res Commun. 1997 Jan 13;230(2):448-51. doi: 10.1006/bbrc.1996.5981.
Cytokine induced pancreatic beta-cell destruction seen in Type 1 diabetes and islet graft rejection involves multiple intracellular signaling pathways that directly or indirectly lead to inflammatory damage or programmed cell death. IL-1beta has been shown to stimulate the 12-lipoxygenase pathway product 12-HETE, in RIN m5F cells; however, the precise role of 12-LO activation in mediating cytokine effects is not clear. Since the stress-activated protein kinase, JNK, has been linked to cytokine mediated inflammatory actions, we studied the effect of two LO products, 12-HETE and 15-HETE, on JNK activity. We demonstrate that 1 nM 12-HETE stimulates JNK activity, while 1 nM 15-HETE, the 15-lipoxygenase pathway product, does not. These results suggest 12-HETE is a novel upstream signal for IL-1beta induced JNK activation in RIN m5F cells.
细胞因子诱导的胰腺β细胞破坏见于1型糖尿病和胰岛移植排斥反应，涉及多个细胞内信号通路，这些信号通路直接或间接导致炎症损伤或程序性细胞死亡。已证明白细胞介素-1β（IL-1β）可刺激RIN m5F细胞中12-脂氧合酶途径产物12-羟基二十碳四烯酸（12-HETE）；然而，12-脂氧合酶（12-LO）激活在介导细胞因子效应中的精确作用尚不清楚。由于应激激活蛋白激酶JNK与细胞因子介导的炎症作用有关，我们研究了两种脂氧合酶产物12-HETE和15-HETE对JNK活性的影响。我们证明1 nM的12-HETE可刺激JNK活性，而1 nM的15-HETE（15-脂氧合酶途径产物）则不能。这些结果表明，12-HETE是IL-1β诱导RIN m5F细胞中JNK激活的一种新的上游信号。
