Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA antibody

被引：64

作者：

Takeda, Y

Takeno, M

Iwasaki, M

Kobayashi, H

Kirino, Y

Ueda, A

Nagahama, K

Aoki, I

Ishigatsubo, Y

机构：

[1] Yokohama City Univ, Grad Sch Med, Dept Internal Med & Clin Immunol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[2] Dept Pathol, Yokohama, Kanagawa, Japan

来源：

CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 2004年 / 138卷 / 02期

关键词：

haem oxygenase-1 (HO-1); MRL/lpr; inducible nitric oxide synthase (iNOS); interferon-gamma (IFN-gamma);

D O I：

10.1111/j.1365-2249.2004.02594.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

There is accumulating evidence that haem oxygenase (HO)-1 plays a protective role in various disorders. The beneficial efficacy of HO-1 induction therapy has been shown in renal diseases such as glomerulonephritis, interstitial nephritis and drug induced nephrotoxicity. However, involvement of HO-1 in the development of autoimmune renal diseases remains uncertain. To assess the clinical efficacy of HO-1 induction therapy for lupus glomerulonephritis, MRL/lpr mice were intraperitoneally injected with 100 mumol/kg hemin, a potent HO-1 inducer, or PBS as controls, once a week from 6 weeks of age to 21-24 weeks-old. We found that treatment with hemin led to a significant reduction of proteinuria and remarkable amelioration of glomerular lesions accompanied by decreased immune depositions. In addition, the circulating IgG anti-double-stranded DNA antibody level was significantly decreased in hemin treated mice when compared with controls. A single intraperitoneal injection with hemin resulted in reduction of inducible nitric oxide synthase expression in the kidney and spleen, and serum interferon-gamma level. Our results suggest that HO-1 induction therapy ameliorates lupus nephritis by suppressing nitric oxide (NO) dependent inflammatory responses and attenuating production of pathogenic autoantibodies.

引用

页码：237 / 244

页数：8

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