TY - JOUR
T1 - Tyrosine kinase inhibitors, genistein and herbimycin A, do not block interleukin-one β-induced activation of NF-κB in rat mesangial cells
AU - Tetsuka, Toshifumi
AU - Srivastava, Sunil K.
AU - Morrison, Aubrey R.
N1 - Funding Information:
This work was supported by U.S. Public Health Award PO 38111. Dr. Tetsuka is a recipient of a NKF matching fellowship award.
PY - 1996/1/26
Y1 - 1996/1/26
N2 - We have previously demonstrated that interleukin-oneβ (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.
AB - We have previously demonstrated that interleukin-oneβ (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.
UR - http://www.scopus.com/inward/record.url?scp=0030050143&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1996.0144
DO - 10.1006/bbrc.1996.0144
M3 - Article
C2 - 8579596
AN - SCOPUS:0030050143
SN - 0006-291X
VL - 218
SP - 808
EP - 812
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -