THE STRESS-ACTIVATED C-JUN PROTEIN-KINASE (JNK) IS STIMULATED BY LIPOXYGENASE PATHWAY PRODUCT 12-HETE IN RIN M5F CELLS

Cytokine induced pancreatic beta-cell destruction seen in Type 1 diabe tes and islet graft rejection involves multiple intracellular signalin g pathways that directly or indirectly lead to inflammatory damage or programmed cell death. IL-1 beta has been shown to stimulate the 12-li poxygenase pathway product 12-HETE, in RIN m5F cells; however, the pre cise role of 12-LO activation in mediating cytokine effects is not cle ar. 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-lipo xygenase pathway product, does not. These results suggest 12-HETE is a novel upstream signal for IL-1 beta induced JNK activation in RIN m5F cells. (C) 1997 Academic Press