title: IL-1RI deficiency ameliorates early experimental renal interstitial fibrosis.
abstract: BACKGROUND
  IL-1beta has the potential to promote progressive renal disease by effects on macrophage recruitment and activation or by effects mediated through tubular cell transforming growth factor (TGF)-beta production, previously demonstrated in vitro.
  
  
  METHODS
  The in vivo roles of endogenous IL-1beta and its type I receptor (IL-1RI) in renal fibrosis were studied using wild-type C57BL/6 mice, IL-1beta(-/-) and IL-1RI(-/-) mice with unilateral ureteric obstruction.
  
  
  RESULTS
  After 7 days, IL-1RI(-/-) mice (IL-1alpha and IL-1beta deficient) were protected from injury and collagen accumulation. IL-1beta(-/-) mice demonstrated some histological protection, but no reduction in alpha1(1) procollagen mRNA or biochemically measured collagen accumulation. Compared with obstructed kidneys from wild-type mice, TGF-beta1 mRNA was reduced in IL-1RI(-/-) mice (with trends to reduced TGF-beta2 and TGF-beta3). Expression of a downstream TGF-beta effector, connective tissue growth factor, was decreased in IL-1RI(-/-) mice. IL-1RI(-/-) mice exhibited less tubulointerstitial apoptosis compared with wild-type mice. Macrophage infiltration and adhesion molecule mRNA expression was unchanged in IL-1beta(-/-) or IL-1RI(-/-) mice. While TNF expression was similar to wild-type mice, IFN-gamma expression was reduced in both IL-1beta(-/-) and IL-1RI(-/-) mice. IL-1RI(-/-) mice at 14 days showed a catch-up in fibrosis compared with wild-type mice.
  
  
  CONCLUSIONS
  IL-1/IL-1RI interactions are profibrotic in renal fibrosis. IL-1RI(-/-) mice were more protected at an early stage, associated with changes in TGF-beta and downstream mediators of fibrosis, but independent of the presence of infiltrating macrophages.
authors.affiliation: Department of Medicine, Centre for Inflammatory Diseases, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Lynelle K
authors.initials: LK
authors.lastname: Jones
authors.forename: Kim M
authors.initials: KM
authors.lastname: O'Sullivan
authors.forename: Timothy
authors.initials: T
authors.lastname: Semple
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kuligowski
authors.forename: Kei
authors.initials: K
authors.lastname: Fukami
authors.forename: Frank Y
authors.initials: FY
authors.lastname: Ma
authors.forename: David J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Holdsworth
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000209:etiology; D007668:Kidney / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency* / Q000502:physiology
chemical_list: D053573:Receptors, Interleukin-1 Type I