Suppression of experimental crescentic glomerulonephritis by peroxisome proliferator-activated receptor (PPAR)gamma activators.
BACKGROUND
It has been recently reported that peroxisome proliferator-activated receptors (PPARs)gamma exist in various tissues and that they exibit anti-inflammatory effects.


METHODS
We investigated the effects of PPARgamma activators on the development of crescentic glomerulonephritis. Crescentic glomerulonephritis was induced by the injection of rabbit anti-rat glomerular basement membrane antibody in WKY rats.


RESULTS
Administration of troglitazone suppressed urinary protein excretion and crescent formation as indicated by crescent scores. Pioglitazone, a PPARgamma activator, mimicked the effect of troglitazone, but bezafibrate, a PPARalpha-activator, did not. Immunohistology revealed that troglitazone and pioglitazone inhibited the infiltration of ED-1-positive monocyte/macrophages and CD8-positive cells into glomeruli.


CONCLUSIONS
In the present study, we demonstrated that PPARgamma activators exert antinephritic effects by suppressing the recruitment of inflammatory cells via a PPARgamma-dependent mechanism.
Third Department of Internal Medicine, Yamanashi Medical University, 1110 Tamaho, Nakakoma, Yamanashi 409-3898, Japan. kazutaka@swallow.res.yamanashi-med.ac.jp
Kazutaka
K
Haraguchi
Hiroki
H
Shimura
Toshimasa
T
Onaya
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000906:Antibodies / Q000008:administration & dosage; D001323:Autoantibodies; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002839:Chromans / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007700:Kinetics; D008264:Macrophages / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000473:pathology; D000077205:Pioglitazone; D011507:Proteinuria; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000502:physiology*; D045162:Thiazolidinediones / Q000627:therapeutic use; D014157:Transcription Factors / Q000187:drug effects* / Q000502:physiology*; D000077288:Troglitazone
D000906:Antibodies; D001323:Autoantibodies; D002839:Chromans; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; C051951:antiglomerular basement membrane antibody; D000077288:Troglitazone; D000077205:Pioglitazone