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Withaferin A inhibits iNOS expression and nitric oxide production by Akt inactivation and down-regulating LPS-induced activity of NF-κB in RAW 264.7 cells

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Author(s)
Jung Hwa OhTae-Jin LeeJong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
Park, Jong WookKwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
European Journal of Pharmacology
Issued Date
2008
Volume
599
Issue
1-3
Abstract
Induction of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production is thought to
have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In Raw 264.7 cells
stimulated with lipopolysaccharide (LPS) to mimic inflammation, withaferin A inhibited LPS-induced
expression of both iNOS protein and mRNA in a dose-dependent manner. To investigate the mechanism by
which withaferin A inhibits iNOS gene expression, we examined activation of mitogen-activated protein
kinases (MAPKs) and Akt in Raw 264.7 cells. We did not observe any significant changes in the
phosphorylation of p38 MAPK in cells treated with LPS alone or LPS plus withaferin A. However, LPSinduced
Akt phosphorylation was markedly inhibited by withaferin A, while the phosphorylation of p42/p44
extracellular signal-regulated kinases (ERKs) was slightly inhibited by withaferin A treatment. Withaferin A
prevented IκB phosphorylation, blocking the subsequent nuclear translocation of nuclear factor-κB (NF-κB)
and inhibiting its DNA binding activity. LPS-induced p65 phosphorylation, which is mediated by extracellular
signal-regulated kinase (ERK) and Akt pathways, was attenuated by withaferin A treatment. Moreover, LPSinduced
NO production and NF-κB activation were inhibited by SH-6, a specific inhibitor of Akt. Taken
together, these results suggest that withaferin A inhibits inflammation through inhibition of NO production
and iNOS expression, at least in part, by blocking Akt and subsequently down-regulating NF-κB activity.
Keimyung Author(s)(Kor)
박종욱
권택규
Publisher
School of Medicine
Citation
Jung Hwa Oh et al. (2008). Withaferin A inhibits iNOS expression and nitric oxide production by Akt inactivation
and down-regulating LPS-induced activity of NF-κB in RAW 264.7 cells. European Journal of Pharmacology, 599(1–3), 11–17. doi: 10.1016/j.ejphar.2008.09.017
Type
Article
ISSN
0014-2999
Source
https://www.sciencedirect.com/science/article/pii/S0014299908009527?via%3Dihub
DOI
10.1016/j.ejphar.2008.09.017
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35681
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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