title: RANTES deficiency attenuates autoantibody-induced glomerulonephritis.
abstract: Experimental autoimmune nephritis in mice and spontaneous lupus nephritis are both associated with elevated expression of several chemokines in the kidneys. Nevertheless, the role that different chemokines play in mediating renal inflammation is far from complete. This study focuses on elucidating the functional role of RANTES, a chemokine that has been noted to be hyper-expressed within the kidneys, both in experimental renal disease as well as in spontaneous lupus nephritis. To elucidate if RANTES was essential for immune-mediated glomerulonephritis, DBA/1 mice that are highly sensitive to nephrotoxic serum nephritis were rendered RANTES-deficient and then tested for disease susceptibility. Nephritis-sensitive DBA/1 mice expressed more RANTES within the diseased kidneys. Compared to wild-type DBA/1 mice, RANTES-deficient DBA/1 mice developed significantly less proteinuria, azotemia, and renal inflammation, with reduced crescent formation and tubulo-interstitial nephritis. These findings indicate that RANTES ablation attenuates immune-mediated nephritis and suggest that this chemokine could be a potential therapeutic target in these diseases.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Mail Code 8884, Y8.212, 5323 Harry Hines Boulevard, Dallas, TX 75390-8884, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Xie
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Fu
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Qin
authors.forename: Geetha
authors.initials: G
authors.lastname: Jonnala
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Hong W
authors.initials: HW
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Maldonado
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D018946:Chemokine CCL5 / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology*; D007668:Kidney / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011507:Proteinuria; D011817:Rabbits
chemical_list: D001323:Autoantibodies; D018946:Chemokine CCL5