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Title: Artemisolide is a typical inhibitor of I{kappa}B kinase {beta} targeting cysteine-179 residue and down-regulates NF-{kappa}B-dependent TNF-{alpha} expression in LPS-activated macrophages

Abstract

Nuclear factor (NF)-{kappa}B regulates a central common signaling for immunity and cell survival. Artemisolide (ATM) was previously isolated as a NF-{kappa}B inhibitor from a plant of Artemisia asiatica. However, molecular basis of ATM on NF-{kappa}B activation remains to be defined. Here, we demonstrate that ATM is a typical inhibitor of I{kappa}B kinase {beta} (IKK{beta}), resulting in inhibition of lipopolysaccharide (LPS)-induced NF-{kappa}B activation in RAW 264.7 macrophages. ATM inhibited the kinase activity of highly purified IKK{beta} and also LPS-induced IKK activity in the cells. Moreover, the effect of ATM on IKK{beta} activity was completely abolished by substitution of Cys-179 residue of IKK{beta} to Ala residue, indicating direct targeting site of ATM. ATM could inhibit I{kappa}B{alpha} phosphorylation in LPS-activated RAW 264.7 cells and subsequently prevent NF-{kappa}B activation. Further, we demonstrate that ATM down-regulates NF-{kappa}B-dependent TNF-{alpha} expression. Taken together, this study provides a pharmacological potential of ATM in NF-{kappa}B-dependent inflammatory disorders.

Authors:
; ; ;  [1];  [2];  [3]; ; ;  [1];  [1]
  1. College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)
  2. Korea Research Institute of Chemical Technology, Taejon 305-600 (Korea, Republic of)
  3. College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)
Publication Date:
OSTI Identifier:
21032899
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 361; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2007.07.069; PII: S0006-291X(07)01506-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CYSTEINE; IMMUNITY; INFLAMMATION; MACROPHAGES; PHOSPHORYLATION; PLANTS; RESIDUES

Citation Formats

Kim, Byung Hak, Lee, Jun-Young, Seo, Jee Hee, Lee, Hwa Young, Ryu, Shi Yong, Ahn, Byung Woo, Lee, Chong-Kil, Hwang, Bang Yeon, Han, Sang-Bae, and Kim, Youngsoo. Artemisolide is a typical inhibitor of I{kappa}B kinase {beta} targeting cysteine-179 residue and down-regulates NF-{kappa}B-dependent TNF-{alpha} expression in LPS-activated macrophages. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.07.069.
Kim, Byung Hak, Lee, Jun-Young, Seo, Jee Hee, Lee, Hwa Young, Ryu, Shi Yong, Ahn, Byung Woo, Lee, Chong-Kil, Hwang, Bang Yeon, Han, Sang-Bae, & Kim, Youngsoo. Artemisolide is a typical inhibitor of I{kappa}B kinase {beta} targeting cysteine-179 residue and down-regulates NF-{kappa}B-dependent TNF-{alpha} expression in LPS-activated macrophages. United States. https://doi.org/10.1016/j.bbrc.2007.07.069
Kim, Byung Hak, Lee, Jun-Young, Seo, Jee Hee, Lee, Hwa Young, Ryu, Shi Yong, Ahn, Byung Woo, Lee, Chong-Kil, Hwang, Bang Yeon, Han, Sang-Bae, and Kim, Youngsoo. 2007. "Artemisolide is a typical inhibitor of I{kappa}B kinase {beta} targeting cysteine-179 residue and down-regulates NF-{kappa}B-dependent TNF-{alpha} expression in LPS-activated macrophages". United States. https://doi.org/10.1016/j.bbrc.2007.07.069.
@article{osti_21032899,
title = {Artemisolide is a typical inhibitor of I{kappa}B kinase {beta} targeting cysteine-179 residue and down-regulates NF-{kappa}B-dependent TNF-{alpha} expression in LPS-activated macrophages},
author = {Kim, Byung Hak and Lee, Jun-Young and Seo, Jee Hee and Lee, Hwa Young and Ryu, Shi Yong and Ahn, Byung Woo and Lee, Chong-Kil and Hwang, Bang Yeon and Han, Sang-Bae and Kim, Youngsoo},
abstractNote = {Nuclear factor (NF)-{kappa}B regulates a central common signaling for immunity and cell survival. Artemisolide (ATM) was previously isolated as a NF-{kappa}B inhibitor from a plant of Artemisia asiatica. However, molecular basis of ATM on NF-{kappa}B activation remains to be defined. Here, we demonstrate that ATM is a typical inhibitor of I{kappa}B kinase {beta} (IKK{beta}), resulting in inhibition of lipopolysaccharide (LPS)-induced NF-{kappa}B activation in RAW 264.7 macrophages. ATM inhibited the kinase activity of highly purified IKK{beta} and also LPS-induced IKK activity in the cells. Moreover, the effect of ATM on IKK{beta} activity was completely abolished by substitution of Cys-179 residue of IKK{beta} to Ala residue, indicating direct targeting site of ATM. ATM could inhibit I{kappa}B{alpha} phosphorylation in LPS-activated RAW 264.7 cells and subsequently prevent NF-{kappa}B activation. Further, we demonstrate that ATM down-regulates NF-{kappa}B-dependent TNF-{alpha} expression. Taken together, this study provides a pharmacological potential of ATM in NF-{kappa}B-dependent inflammatory disorders.},
doi = {10.1016/j.bbrc.2007.07.069},
url = {https://www.osti.gov/biblio/21032899}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 361,
place = {United States},
year = {Fri Sep 28 00:00:00 EDT 2007},
month = {Fri Sep 28 00:00:00 EDT 2007}
}