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 language | English |
|---|---|
| Pages (from-to) | 595-600 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 328 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2005 Mar 11 |
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Keywords
- 5-Lipoxygenase
- Inflammation
- Interferon-γ
- NDGA
- STAT
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Nordihydroguaiaretic acid inhibits IFN-γ-induced STAT tyrosine phosphorylation in rat brain astrocytes. / Jeon, Sae B.; Ji, Kyung A.; You, Hye J.; Kim, Jae-Hong; Jou, Ilo; Joe, Eun H.
In: Biochemical and Biophysical Research Communications, Vol. 328, No. 2, 11.03.2005, p. 595-600.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nordihydroguaiaretic acid inhibits IFN-γ-induced STAT tyrosine phosphorylation in rat brain astrocytes
AU - Jeon, Sae B.
AU - Ji, Kyung A.
AU - You, Hye J.
AU - Kim, Jae-Hong
AU - Jou, Ilo
AU - Joe, Eun H.
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
UR - http://www.scopus.com/inward/record.url?scp=13444249682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13444249682&partnerID=8YFLogxK
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 - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 2
ER -