Mycophenolate mofetil reduces renal cortical inducible nitric oxide synthase mRNA expression and diminishes glomerulosclerosis in MRL/Ipr mice

Chun Chen Yu, Chih Wei Yang, Mai Szu Wu, Yi Ching Ko, Chiung Tseng Huang, Jenn Jye Hong, Chiu Ching Huang

研究成果: 雜誌貢獻文章

41 引文 斯高帕斯(Scopus)

摘要

Overexpression of inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus glomerulonephritis. Mycophenolate mofetil (MMF), a novel immunosuppressive agent, is currently used in organ transplantation and under evaluation for treatment of autoimmune disorders. Mycophenolic acid, the active metabolite of MMF, has been shown to suppress cytokine-induced nitric oxide production in vitro. The aim of this study was to evaluate the effect of MMF on the expression of renal cortical iNOS mRNA and protection against glomerulonephritis in MRL/Ipr mice. Three-month-old MRL/Ipr mice (n = 6) displaying clinical symptoms of glomerulonephritis were treated for 3 months with MMF (90 mg/kg/day) dissolved in a vehicle. Controls were age- and sex-matched mice (n = 6) that received the vehicle alone. By reverse-transcription competitive polymerase chain reaction, we found that the renal cortical iNOS/β-actin mRNA ratio was reduced by 30.8% (P <.05) in MMF-treated mice. Furthermore, MMF significantly reduced urinary nitrite production and degree of glomerulosclerosis. The glomerular volume was reduced by 17.5% (P <.001). Proteinuria was also significantly reduced in the MMF-treated group. However, by electrophoretic mobility shift assay, the nuclear binding of nuclear factor-κB (NF-κB) was not affected by MMF treatment. We conclude that in addition to its immunosuppressive action, MMF may reduce renal cortical iNOS mRNA expression and diminish glomerulosclerosis in MRL/Ipr mice independent of modulation of the NF-κB pathway.

原文英語
頁(從 - 到)69-77
頁數9
期刊Journal of Laboratory and Clinical Medicine
138
發行號1
DOIs
出版狀態已發佈 - 2001
對外發佈Yes

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

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