Effect of the tyrosine kinase inhibitor, genistein, on interleukin-1 stimulated PGE2 production in mesangial cells.
Prostaglandin production and cAMP formation are two signaling pathways identified for IL-1, though neither adequately account for the multitude of effects of IL-1. To investigate the role of tyrosine phosphorylation in IL-1 signaling, we used the tyrosine kinase inhibitor, genistein. At 10-30 micrograms/ml, genistein blocked IL-1 stimulated prostaglandin production and induction of prostaglandin endoperoxide synthase (PES) in glomerular mesangial cells maintained in 10% serum. Addition of genistein hours after IL-1 addition also halted further PGE2 synthesis. Genistein failed to block PES activity in vitro, indicating it was not acting as a PES inhibitor. Overall these data suggest that tyrosine phosphorylation may be a required event for IL-1 stimulation of PGE2 and PES activity, either directly as part of IL-1 signaling, or indirectly as part of a serum/PDGF competence effect on mesangial cells.
Coyne
D W
DW
Washington University School of Medicine, Department of Medicine, St. Louis, Missouri 63110.
Morrison
A R
AR
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D046508:Culture Techniques; D015232:Dinoprostone / Q000096:biosynthesis*; D019833:Genistein; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000201:enzymology; D007376:Interleukin-2 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology*; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats
D007376:Interleukin-2; D007529:Isoflavones; D019833:Genistein; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases; D015232:Dinoprostone