Chemical induction of HO‐1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti‐dsDNA antibody
Chemical induction of HO‐1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti‐dsDNA antibody
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DOI：
10.1111/j.1365-2249.2004.02594.x
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发表时间：
2004-11
影响因子：
4.6
通讯作者：
Y. Takeda;M. Takeno;M. Iwasaki;H. Kobayashi;Y. Kirino;A. Ueda;K. Nagahama;I. Aoki;Y. Ishigatsubo
中科院分区：
文献类型：
--
作者：
Y. Takeda;M. Takeno;M. Iwasaki;H. Kobayashi;Y. Kirino;A. Ueda;K. Nagahama;I. Aoki;Y. Ishigatsubo
越来越多的证据表明血红素加氧酶（HO）‐1在多种疾病中起保护作用。HO‐1诱导治疗在肾小球肾炎、间质性肾炎和药物性肾毒性等肾脏疾病中已显示出有益的疗效。然而，HO‐1参与自身免疫性肾脏疾病的发展仍不确定。为了评估HO‐1诱导治疗狼疮肾小球肾炎的临床疗效，从6周龄至21-24周龄，MRL/lpr小鼠每周1次腹腔注射100µmol/kg血红素（一种强效HO‐1诱导剂）或PBS作为对照。我们发现，用血红素治疗导致蛋白尿显著减少，肾小球病变显著改善，并伴有免疫沉积减少。此外，与对照组相比，血红素处理小鼠的循环IgG抗双链DNA抗体水平显著降低。单次腹腔注射血红素导致肾脏和脾脏诱导型一氧化氮合酶表达降低，血清干扰素γ水平降低。我们的研究结果表明，HO‐1诱导治疗通过抑制一氧化氮（NO）依赖性炎症反应和减少致病性自身抗体的产生来改善狼疮性肾炎。
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 µmol/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‐γ 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.