title: Corticosteroids worsen proteinuria and increase intraglomerular signaling by NF-ĸB in a model of membranous glomerulonephritis.
abstract: OBJECTIVE
  Passive Heymann nephritis (PHN) is a model of human membranous glomerulonephritis characterized by heavy proteinuria. We have recently demonstrated activation of NF-κB by podocytes in this model. In this study, therefore, we have determined whether dexamethasone (DEX) and pyrrolidine dithiocarbamate (PDTC), therapies that inhibit NF-κB, influence proteinuria.
  
  
  METHODS
  Twenty-one days after induction of PHN, rats were divided into three groups: group 1 received saline, group 2 received DEX for 7 days, and group 3 received PDTC for 7 days. The effects of these drugs on activation of NF-κB and proteinuria were then determined.
  
  
  RESULTS
  DEX administration was associated with a very significant increase in proteinuria, whereas PDTC produced a slight decrease. Within the glomerulus, both agents were associated with increased levels of IL-1β mRNA and protein, compared with untreated rats, and there was increased nuclear localization of p50 in both of the treated groups. Neither agent, therefore, inhibited NF-κB activation within the glomerulus. Both agents produced a decrease in the systemic anti-sheep Ig immune response, and there was reduced interstitial αβ T-cell infiltration compared with controls.
  
  
  CONCLUSIONS
  These data suggest that agents predicted to inhibit NF-κB might have opposing effects in membranous glomerulonephritis. The use of steroids to treat membranous glomerulonephritis, therefore, might produce unpredictable results, depending on whether suppression of the systemic immune response or inflammatory events within the kidney is more important in a particular patient.
authors.affiliation: Department of Nephrology, Austin Health, Heidelberg, Vic, Australia.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Mudge
authors.forename: Kathy
authors.initials: K
authors.lastname: Paizis
authors.forename: Russell B
authors.initials: RB
authors.lastname: Auwardt
authors.forename: Vicki
authors.initials: V
authors.lastname: Levidiotis
authors.forename: Scott A
authors.initials: SA
authors.lastname: Fraser
authors.forename: David A
authors.initials: DA
authors.lastname: Power
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D011507:Proteinuria / Q000139:chemically induced; D011759:Pyrrolidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects*; D013859:Thiocarbamates / Q000627:therapeutic use*
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D003907:Dexamethasone