title: Opposing effects of interleukin-1 and transforming growth factor-beta on the regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 expression by human mesangial cells.
abstract: Several proteases have been implicated in regulating the turnover of mesangial matrix within the glomerulus. One such group, the plasminogen activators (PAs) and their inhibitor, PA inhibitor type-1 (PAI-1), is produced by glomerular cells with altered expression during nephritis. We report the effect of IL-1 and transforming growth factor-beta (TGF-beta) and a combination of the two cytokines on the secretion of tissue-type PA (t-PA) and PAI-1 from human mesangial cells. IL-1 significantly downregulates PAI-1 production and upregulates t-PA over a range of concentrations (1-10 U/ml), while TGF-beta (0.5-10 ng/ml) has the opposite effect. The combined effect of these factors is that TGF-beta attenuates the increase in t-PA and decrease in PAI-1 expression caused by IL-1, and has a dominant effect upon their secretion, thus decreasing t-PA and increasing PAI-1. These findings contribute to our understanding of fibrinolysis and tissue remodelling within the glomerular mesangium during the course of nephritis.
authors.affiliation: Department of Molecular and Cell Biology, University of Aberdeen, UK. h.m.wilson@abdn.ac.uk
authors.forename: H M
authors.initials: HM
authors.lastname: Wilson
authors.forename: N E
authors.initials: NE
authors.lastname: Haites
authors.forename: N A
authors.initials: NA
authors.lastname: Booth
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D015342:DNA Probes / Q000235:genetics; D004347:Drug Interactions; D005342:Fibrinolysis; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D009393:Nephritis / Q000209:etiology / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology
chemical_list: D015342:DNA Probes; D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D010959:Tissue Plasminogen Activator