Guan Z, Buckman S Y, Baier L D, Morrison A R
Department of Molecular Biology and Pharmacology and Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Physiol. 1998 Apr;274(4):F673-9. doi: 10.1152/ajprenal.1998.274.4.F673.
The inflammatory cytokine interleukin-1 beta (IL-1 beta) induces both cyclooxygenase-2 (Cox-2) and the inducible nitric oxide synthase (iNOS) with concomitant release of PGs and nitric oxide (NO) by glomerular mesangial cells. In our current studies, we determine whether insulin and IGF-I are involved in the signal transduction mechanisms resulting in IL-1 beta-induced NO and PGE2 biosynthesis in renal mesangial cells. We demonstrate that both insulin and IGF-I increase IL-1 beta-induced Cox-2 and iNOS protein expression, which in turn enhance PGE2 and NO production. Our data also indicate that both insulin and IGF-I enhance IL-1 beta-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation and SAPK activation. These findings implicate the possible role of the MAPK pathway in mediating the effects of insulin and IGF-I on the upregulation of cytokine-stimulated NO and PG biosynthesis. Together, our results indicate that IGF-I and insulin may function to modulate the renal inflammatory process.
炎性细胞因子白细胞介素-1β（IL-1β）可诱导肾小球系膜细胞产生环氧化酶-2（Cox-2）和诱导型一氧化氮合酶（iNOS），同时伴有PGs和一氧化氮（NO）的释放。在我们目前的研究中，我们确定胰岛素和IGF-I是否参与导致肾系膜细胞中IL-1β诱导的NO和PGE2生物合成的信号转导机制。我们证明，胰岛素和IGF-I均增加IL-1β诱导的Cox-2和iNOS蛋白表达，进而增强PGE2和NO的产生。我们的数据还表明，胰岛素和IGF-I均增强IL-1β诱导的p38丝裂原活化蛋白激酶（MAPK）磷酸化和SAPK激活。这些发现提示MAPK途径可能在介导胰岛素和IGF-I对细胞因子刺激的NO和PG生物合成上调的作用中发挥作用。总之，我们的结果表明IGF-I和胰岛素可能起到调节肾脏炎症过程的作用。
