title: Blockade of the kinin B1 receptor ameloriates glomerulonephritis.
abstract: Severe inflammation characterizes rapidly progressive glomerulonephritides, and expression of the kinin B1 receptor (B1R) associates with inflammation. Delayed B1R blockade reduces renal inflammation in a model of unilateral ureteral obstruction, but whether B1R modulates the pathophysiology of glomerulonephritides is unknown. Here, we observed an association of B1R protein expression and inflammation, in both glomeruli and the renal interstitium, in biopsies of patients with glomerulonephritides, Henoch-Schönlein purpura nephropathy, and ANCA-associated vasculitis. In the nephrotoxic serum-induced glomerulonephritis model, we observed upregulation of the B1R receptor; treatment with a B1R antagonist beginning 2 weeks after the onset of disease reduced both glomerular and tubular lesions and improved renal function. B1R blockade reduced renal chemokine expression and macrophage accumulation. Collectively, our data demonstrate that blockade of the kinin B1R has significant potential for the treatment of glomerulonephritis.
authors.affiliation: INSERM, U858/I2MR, Department of Renal and Cardiac Remodeling, Team 5, 31432 Toulouse Cedex 4, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
authors.forename: Julien
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Stéphane
authors.initials: S
authors.lastname: Decramer
authors.forename: Flavio
authors.initials: F
authors.lastname: Bandin
authors.forename: Eric
authors.initials: E
authors.lastname: Neau
authors.forename: David J
authors.initials: DJ
authors.lastname: Salant
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.forename: Joao-Bosco
authors.initials: JB
authors.lastname: Pesquero
authors.forename: Joost-Peter
authors.initials: JP
authors.lastname: Schanstra
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Bascands
mesh_terms: D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001706:Biopsy; D065169:Bradykinin B1 Receptor Antagonists; D018925:Chemokines / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004149:Dioxoles / Q000494:pharmacology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D011695:IgA Vasculitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D012189:Retrospective Studies; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C487113:2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide; D065169:Bradykinin B1 Receptor Antagonists; D018925:Chemokines; D004149:Dioxoles; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D013449:Sulfonamides; D003404:Creatinine
references.citation: J Am Soc Nephrol. 2000 Jan;11(1):152-176
references.pmid: 10616852
references.citation: Regul Pept. 2009 Jan 8;152(1-3):67-72
references.pmid: 18977249
references.citation: Mol Pharmacol. 1999 Aug;56(2):325-33
references.pmid: 10419551
references.citation: Am J Pathol. 2005 Nov;167(5):1207-19
references.pmid: 16251406
references.citation: J Immunol. 1996 Jan 1;156(1):269-74
references.pmid: 8598472
references.citation: J Immunol. 2004 Feb 15;172(4):2542-8
references.pmid: 14764727
references.citation: J Leukoc Biol. 2000 Nov;68(5):587-92
references.pmid: 11073095
references.citation: Lancet. 2002 Aug 17;360(9332):535-41
references.pmid: 12241658
references.citation: Eur J Pharmacol. 2003 Jan 26;460(1):75-83
references.pmid: 12535863
references.citation: Kidney Int. 1999 Apr;55(4):1319-26
references.pmid: 10200996
references.citation: Br J Pharmacol. 2007 Sep;152(2):280-7
references.pmid: 17618300
references.citation: J Clin Invest. 2002 Aug;110(3):371-9
references.pmid: 12163456
references.citation: J Clin Invest. 2009 May;119(5):1286-97
references.pmid: 19381017
references.citation: J Pharmacol Exp Ther. 2004 May;309(2):661-9
references.pmid: 14747609
references.citation: FEBS Lett. 1989 Apr 24;247(2):189-92
references.pmid: 2541011
references.citation: J Clin Invest. 1999 Jan;103(1):73-80
references.pmid: 9884336
references.citation: Curr Med Chem. 2008;15(5):448-58
references.pmid: 18289000
references.citation: J Am Soc Nephrol. 2008 Mar;19(3):527-37
references.pmid: 18235094
references.citation: Int Immunopharmacol. 2009 Jun;9(6):653-7
references.pmid: 19010452
references.citation: J Exp Med. 1997 Apr 7;185(7):1371-80
references.pmid: 9104823
references.citation: Pharmacol Rev. 2005 Mar;57(1):27-77
references.pmid: 15734727
references.citation: FASEB J. 2009 Jan;23(1):134-42
references.pmid: 18809736
references.citation: Nat Med. 2009 Jul;15(7):788-93
references.pmid: 19561616
references.citation: Trends Pharmacol Sci. 2006 Dec;27(12):646-51
references.pmid: 17056130
references.citation: Br J Pharmacol. 2008 Jul;154(6):1276-86
references.pmid: 18536758
references.citation: Pharmacol Rev. 1980 Mar;32(1):1-46
references.pmid: 7015371
references.citation: Am J Pathol. 2000 Mar;156(3):879-88
references.pmid: 10702405
references.citation: Curr Opin Pharmacol. 2009 Apr;9(2):125-31
references.pmid: 19124274
references.citation: J Neurosci. 2008 Mar 12;28(11):2856-63
references.pmid: 18337416
references.citation: J Am Soc Nephrol. 2000 Jul;11(7):1208-1215
references.pmid: 10864576
references.citation: Kidney Int. 2004 Aug;66(2):542-57
references.pmid: 15253705
references.citation: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8140-5
references.pmid: 10859349
references.citation: J Clin Invest. 1998 May 15;101(10):2080-91
references.pmid: 9593764
references.citation: Immunopharmacology. 1995 Jun;30(1):1-26
references.pmid: 7591710
references.citation: J Biol Chem. 2000 Apr 28;275(17):12475-80
references.pmid: 10777533
references.citation: Kidney Int. 1998 Dec;54(6):1888-98
references.pmid: 9853254