The essential role of Oct-2 in LPS-induced expression of iNOS in RAW 264.7 macrophages and its regulation by trichostatin A

Shao Chun Lu, Hsiao Wen Wu, Yen Jen Lin, Shwu Fen Chang

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


This article reports on a study of the effect of trichostatin A (TSA), an inhibitor of histone deacetylase, on lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) in RAW 264.7 macrophages and its underlying mechanisms. TSA pretreatment potently diminishes LPS-stimulated nitric oxide (NO) release and both mRNA and protein levels of iNOS in macrophages. The effects of TSA and LPS on transcription factors binding to two LPS-responsive elements within the iNOS promoter, one binding the NF-κB site and the other the octamer element, were investigated. Results show that TSA did not alter the LPS-activated NF-κB activity demonstrated by the nuclear translocation of p50 and p65 and by a NF-κB-driven reporter gene expression system. In addition, neither TSA nor LPS changed the expression of Oct-1, a ubiquitously expressed octamer binding protein. However, TSA suppressed the LPS-induced expression of Oct-2, another octamer binding protein, at both mRNA and protein levels. Chromatin immunoprecipitation assays revealed that binding of Oct-2 to the iNOS promoter was enhanced by LPS treatment; however, pretreatment with TSA resulted in loss of this binding. Moreover, forced expression of Oct-2 by transfection of pCG-Oct-2 plasmid restored the TSA-suppressed iNOS expression elevated by LPS stimulation, further indicating that Oct-2 activation is a crucial step for transcriptional activation of the iNOS gene in response to LPS stimulation in macrophages. This study demonstrates that TSA diminishes iNOS expression in LPS-treated macrophages by inhibiting Oct-2 expression and thus reducing the production of NO.

Original languageEnglish
Pages (from-to)C1133-C1139
JournalAmerican Journal of Physiology - Cell Physiology
Issue number5
Publication statusPublished - May 2009


  • Inducible nitric oxide synthase
  • Lipopolysaccharide
  • Macrophage

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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