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

Clin Exp Immunol. 2004 Nov;138(2):237-44. doi: 10.1111/j.1365-2249.2004.02594.x.

Abstract

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 micromol/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Cells, Cultured
  • Cytokines / analysis
  • DNA / immunology*
  • Female
  • Heme Oxygenase (Decyclizing) / immunology*
  • Heme Oxygenase-1
  • Hemin / administration & dosage
  • Hemin / immunology
  • Immunoglobulin G / immunology
  • Injections, Intraperitoneal
  • Kidney / immunology
  • Kidney Glomerulus / immunology
  • Lupus Nephritis / immunology*
  • Membrane Proteins
  • Mice
  • Mice, Inbred MRL lpr
  • Nitric Oxide Synthase / analysis*
  • Nitric Oxide Synthase Type II
  • Spleen / immunology

Substances

  • Antibodies, Antinuclear
  • Cytokines
  • Immunoglobulin G
  • Membrane Proteins
  • Hemin
  • DNA
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse