TY - JOUR
T1 - Nordihydroguaiaretic acid inhibits IFN-γ-induced STAT tyrosine phosphorylation in rat brain astrocytes
AU - Jeon, Sae Bom
AU - Ji, Kyung Ae
AU - You, Hye Jin
AU - Kim, Jae Hong
AU - Jou, Ilo
AU - Joe, Eun Hye
N1 - Funding Information:
This work was supported by Korea Science and Engineering Foundation (KOSEF) through the Brain Disease Research Center at Ajou University, and a grant (M103KV010006 03K2201 00650) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea (to E. Joe).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2005/3/11
Y1 - 2005/3/11
N2 - 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.
AB - 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.
KW - 5-Lipoxygenase
KW - Inflammation
KW - Interferon-γ
KW - NDGA
KW - STAT
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U2 - 10.1016/j.bbrc.2005.01.025
DO - 10.1016/j.bbrc.2005.01.025
M3 - Article
C2 - 15694390
AN - SCOPUS:13444249682
VL - 328
SP - 595
EP - 600
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -