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Effect of inducible nitric oxide synthase on apoptosis in Candida-induced acute lung injury

Shigekuni Hosogi1, Yoshinobu Iwasaki, Takahiro Yamada

  • 1Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. hosogi@koto.kpu-m.ac.jp

Biomedical Research (Tokyo, Japan)
|November 11, 2008
PubMed

Insights

Inhibiting inducible nitric oxide synthase (iNOS) with ONO-1714 reduces apoptosis in acute lung injury (ALI). This finding offers a potential therapeutic strategy for improving survival in ALI patients.

Area of Science:

  • Pulmonary Medicine
  • Immunology
  • Cell Biology

Background:

  • Inducible nitric oxide synthase (iNOS) produces excessive nitric oxide (NO), which aggravates acute lung injury (ALI) via peroxynitrite formation.
  • iNOS and NO play crucial roles in Candida-induced ALI, contributing to epithelial cell apoptosis.
  • Previous studies demonstrated ONO-1714's efficacy in suppressing iNOS expression and ALI in mice.

Purpose of the Study:

  • To investigate the specific effect of NO on alveolar epithelial cell apoptosis in a mouse model of Candida-induced ALI.
  • To determine if inhibiting iNOS-derived NO production impacts apoptosis and disease severity.

Main Methods:

  • Mice with Candida-induced ALI were pretreated with the iNOS inhibitor ONO-1714 or saline.
  • Apoptosis in lung tissues was assessed 24 hours post-infection using TUNEL staining and caspase 3 activity.
  • Gene and protein expression related to apoptosis (FasL, TNF-alpha, Bax) was analyzed.

Main Results:

  • Inhibition of iNOS-derived NO production by ONO-1714 significantly suppressed apoptosis of alveolar epithelial cells.
  • Elevated NO levels correlated with increased FasL, TNF-alpha, and Bax mRNA, promoting apoptosis.
  • ONO-1714 treatment ameliorated Candida-induced ALI and improved survival rates.

Conclusions:

  • iNOS-derived NO is a key mediator of alveolar epithelial cell apoptosis in Candida-induced ALI.
  • Inhibition of iNOS with ONO-1714 offers a promising therapeutic approach for ALI by reducing apoptosis and improving outcomes.

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