Tyrosine Kinase Inhibitors, Genistein and Herbimycin A, Do Not Block Interleukin-1 β-Induced Activation of NF-κB in Rat Mesangial Cells
Tyrosine Kinase Inhibitors, Genistein and Herbimycin A, Do Not Block Interleukin-1 β-Induced Activation of NF-κB in Rat Mesangial Cells
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酪氨酸激酶抑制剂金雀异黄素和除草霉素 A 不会阻断大鼠肾小球系膜细胞中白细胞介素 1 β 诱导的 NF-κB 激活
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
A. Morrison
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文献类型：
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作者：
T. Tetsuka;S. Srivastava;A. Morrison
摘要：我们之前已经证明，白细胞介素 1 β (IL-1β) 能够快速诱导肾系膜细胞中多种蛋白质的酪氨酸磷酸化。两种机制不同的酪氨酸激酶抑制剂金雀异黄素和除草霉素 A 可阻断大鼠系膜细胞中 IL-1β 对环氧合酶 2 (COX-2) 和诱导型一氧化氮合酶 (iNOS) 的诱导。由于 COX-2 和 iNOS 启动子都具有 κB 结合基序，因此我们通过电迁移率位移测定评估了酪氨酸激酶抑制剂对 IL-1β 诱导的核因子 κB (NF-κB) 激活的影响。 IL-1β rapidly induced the translocation of NF-κB in rat mesangial cells.然而，酪氨酸激酶抑制剂金雀异黄素和除草霉素 A 在消除 COX-2 和 iNOS mRNA 表达的浓度下未能阻断 NF-κB 的易位。这些数据表明上游酪氨酸激酶途径可能不是IL-1β诱导的NF-κB激活所必需的，并且酪氨酸激酶途径可能与大鼠系膜细胞中NF-κB激活下游的NF-κB途径汇聚。
Abstract We have previously demonstrated that interleukin-1 β (IL-1β) rapidly induces tyrosine phosphorylation of several proteins in the renal mesangial cell. Two mechanistically distinct tyrosine kinase inhibitors, genistein and herbimycin A, block the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by IL-1β in rat mesangial cells. Since both COX-2 and iNOS promoters have a κB binding motif, we have evaluated the effects of tyrosine kinase inhibitors on IL-1β-induced nuclear factor-κB (NF-κB) activation by electromobility shift assays. IL-1β rapidly induced the translocation of NF-κB in rat mesangial cells. However, the tyrosine kinase inhibitors, genistein and herbimycin A, failed to block the translocation of NF-κB at concentrations which abolish COX-2 and iNOS mRNA expression. These data suggest that an upstream tyrosine kinase pathway may not be required for IL-1β-induced NF-κB activation and that the tyrosine kinase pathway may converge with the NF-κB pathway down-stream of NF-κB activation in rat mesangial cells.