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

Authors
Jeon, SB; Ji, KA; You, HJ; Kim, JH; Jou, I; Joe, EH
Citation
Biochemical and biophysical research communications, 328(2):595-600, 2005
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
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-gamma (IFN-gamma), an important pro-inflammatory cytokine. Therefore, regulation of JAK/STAT signaling should modulate IFN-gamma-mediated inflammation. In this study, we found that nordihydroguaiaretic acid (NDGA), a well-known lipoxygenase (LO) inhibitor, suppressed IFN-gamma-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-gamma was significantly suppressed in the presence of NDGA, as was tyrosine-phosphorylation of JAK and STAT. However, the 5-LO products, leukotriene B(4) (LTB(4)) and leukotriene C(4), were not detected in cells treated with IFN-gamma, 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 LTB(4), were unable to reverse NDGA-driven suppression of STAT activation or affect basal STAT phosphorylation. Taken together, these results suggest that NDGA regulates IFN-gamma-mediated inflammation through mechanisms unrelated to the inhibition of 5-LO.
MeSH terms
AnimalsArachidonate 5-Lipoxygenase/immunologyArachidonate 5-Lipoxygenase/metabolism*Astrocytes/drug effectsAstrocytes/immunologyAstrocytes/metabolism*Brain/drug effectsBrain/immunologyBrain/metabolism*Cells, CulturedDose-Response Relationship, DrugInterferon-gamma/pharmacology*Lipoxygenase InhibitorsMicroglia/drug effectsMicroglia/immunologyMicroglia/metabolism*Nordihydroguaiaretic Acid/pharmacology*Phosphorylation/drug effectsRatsRats, Sprague-DawleySignal Transduction/drug effectsSignal Transduction/physiologyTrans-Activators/immunologyTrans-Activators/metabolism*Tyrosine/immunologyTyrosine/metabolism*
DOI
10.1016/j.bbrc.2005.01.025
PMID
15694390
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
주, 일로조, 은혜
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