Nordihydroguaiaretic acid inhibits IFN-γ-induced STAT tyrosine phosphorylation in rat brain astrocytes

Sae B. Jeon, Kyung A. Ji, Hye J. You, Jae-Hong Kim, Ilo Jou, Eun H. Joe

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8 Citations (Scopus)

Abstract

The Janus kinase (JAK) and signal transducers and activators of transcription (STAT) signal cascades are major pathways that mediate the inflammatory functions of interferon-γ (IFN-γ), an important pro-inflammatory cytokine. Therefore, regulation of JAK/STAT signaling should modulate IFN-γ-mediated inflammation. In this study, we found that nordihydroguaiaretic acid (NDGA), a well-known lipoxygenase (LO) inhibitor, suppressed IFN-γ-induced inflammatory responses in brain astrocytes. In the presence of NDGA, interferon regulatory factor-1 expression was significantly reduced. Expression of monocyte chemotactic protein-1 and interferon-gamma inducible protein-10 mRNA in response to IFN-γ was significantly suppressed in the presence of NDGA, as was tyrosine- phosphorylation of JAK and STAT. However, the 5-LO products, leukotriene B 4 (LTB4) and leukotriene C4, were not detected in cells treated with IFN-γ, indicating that the effect of NDGA seemed to be independent of 5-LO inhibition. In addition, two other 5-LO inhibitors (Rev5901 and AA861) did not mimic the effect of NDGA, and the 5-LO metabolites, 5-hydroxyeicosatetraenoic acid and LTB4, were unable to reverse NDGA-driven suppression of STAT activation or affect basal STAT phosphorylation. Taken together, these results suggest that NDGA regulates IFN-γ-mediated inflammation through mechanisms unrelated to the inhibition of 5-LO.

Original languageEnglish
Pages (from-to)595-600
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume328
Issue number2
DOIs
Publication statusPublished - 2005 Mar 11

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Keywords

  • 5-Lipoxygenase
  • Inflammation
  • Interferon-γ
  • NDGA
  • STAT

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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