Tyrosine kinase inhibitors, genistein and herbimycin A, do not block interleukin-1 beta-induced activation of NF-kappa B in rat mesangial cells.
We have previously demonstrated that interleukin-1 beta (IL-1 beta) 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-1 beta in rat mesangial cells. Since both COX-2 and iNOS promoters have a kappa B binding motif, we have evaluated the effects of tyrosine kinase inhibitors on IL-1 beta-induced nuclear factor-kappa B (NF-kappa B) activation by electromobility shift assays. IL-1 beta rapidly induced the translocation of NF-kappa B in rat mesangial cells. However, the tyrosine kinase inhibitors, genistein and herbimycin A, failed to block the translocation of NF-kappa B 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-1 beta-induced NF-kappa B activation and that the tyrosine kinase pathway may converge with the NF-kappa B pathway down-stream of NF-kappa B activation in rat mesangial cells.
Tetsuka
T
T
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Srivastava
S K
SK
Morrison
A R
AR
D000818:Animals; D001483:Base Sequence; D016227:Benzoquinones; D002451:Cell Compartmentation / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein; D005920:Glomerular Mesangium / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D008297:Male; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000031:analogs & derivatives
D016227:Benzoquinones; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D016328:NF-kappa B; D009687:Nuclear Proteins; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases