Anti-inflammatory and renal protective actions of stanniocalcin-1 in a model of anti-glomerular basement membrane glomerulonephritis.
We have previously shown that stanniocalcin-1 (STC1) inhibits the transendothelial migration of macrophages and T cells, suppresses superoxide generation in macrophages, and attenuates macrophage responses to chemoattractants. To study the effects of STC1 on inflammation, in this study we induced a macrophage- and T-cell-mediated model of anti-glomerular basement membrane disease in STC1 transgenic mice, which display elevated serum STC1 levels and preferentially express STC1 in both endothelial cells and macrophages. We examined the following parameters both at baseline and after anti-glomerular basement membrane antibody treatment: blood pressure; C(3a) levels; urine output; proteinuria; blood urea nitrogen; and kidney C(3) deposition, fibrosis, histological changes, cytokine expression, and number of T cells and macrophages. Compared with wild-type mice, after anti-glomerular basement membrane treatment STC1 transgenic mice exhibited: i) diminished infiltration of inflammatory macrophages in the glomeruli; ii) marked reduction in crescent formation and sclerotic glomeruli; iii) decreased interstitial fibrosis; iv) preservation of kidney function and lower blood pressure; v) diminished C(3) deposition in the glomeruli; and vi) reduced expression of macrophage inhibitory protein-2 and transforming growth factor-beta2 in the kidney. Compared with baseline, wild-type mice, but not STC1 transgenic mice, had higher proteinuria and a marked reduction in urine output. STC1 had minimal effects, however, on both T-cell number in the glomeruli and interstitium and on cytokine expression characteristic of either TH1 or TH2 activation. These data suggest that STC1 is a potent anti-inflammatory and renal protective protein.
Huang
Luping
L
Baylor College of Medicine, Nephrology Division, Department of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Garcia
Gabriela
G
Lou
Yahuan
Y
Zhou
Qin
Q
Truong
Luan D
LD
DiMattia
Gabriel
G
Lan
Xia Ru
XR
Lan
Hui Y
HY
Wang
Yanlin
Y
Sheikh-Hamad
David
D
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D050533:Glomerular Basement Membrane / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology*; D007677:Kidney Function Tests; D051379:Mice; D008822:Mice, Transgenic
D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; C051951:antiglomerular basement membrane antibody; C051795:teleocalcin