AI Article Synopsis

  • IL-13 acts as a significant inhibitor for iNOS expression in rat hepatocytes, reducing both mRNA and protein levels in a concentration-dependent manner.
  • IL-13's most effective dose for inhibiting iNOS was found to be around 5 ng/ml, with no impact on mRNA stability.
  • The study highlighted that IL-13 decreases the binding activity of IRF-1 to the iNOS promoter, thereby suppressing transcriptional activation.

Article Abstract

IL-13 has been reported as one of the major down-regulators of iNOS expression in various tissues and cells. The molecular mechanism of iNOS suppression by IL-13 remains unclear, especially at the transcriptional stage. In this study, we found that IL-13 inhibited the expression of iNOS mRNA, protein, and NO product in a concentration-dependent manner for cytokine-stimulated rat hepatocytes. The most effective dose for IL-13 inhibitory effect is approximately 5 ng/ml. IL-13 also decreased the rat iNOS transcriptional activity by promoter analysis, but had no effect on iNOS mRNA stability. By using TranSignal Protein/DNA Combo Array, we identified cytokine-stimulated IRF-1/ISRE binding that was decreased by the addition of IL-13. Gel shift assay confirmed that IL-13 reduced the IRF-1/ISRE binding at nucleotides -913 to -923 of the rat iNOS promoter. Western blot revealed that IL-13 diminished the relative amount of IRF-1 protein translocated to the nucleus. Our data demonstrate that IL-13 down-regulates the cytokine-induced iNOS transcription by decreasing iNOS specific IRF-1/ISRE binding activity.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025693PMC
http://dx.doi.org/10.1016/j.bbrc.2007.07.203DOI Listing

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Article Synopsis
  • IL-13 acts as a significant inhibitor for iNOS expression in rat hepatocytes, reducing both mRNA and protein levels in a concentration-dependent manner.
  • IL-13's most effective dose for inhibiting iNOS was found to be around 5 ng/ml, with no impact on mRNA stability.
  • The study highlighted that IL-13 decreases the binding activity of IRF-1 to the iNOS promoter, thereby suppressing transcriptional activation.
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