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

Journal Article · Fri Sep 28 04:00:00 EDT 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.07.069· OSTI ID:21032899

Kim, Byung Hak; Lee, Jun-Young; Seo, Jee Hee; Lee, Hwa Young ^[1]; Ryu, Shi Yong ^[2]; Ahn, Byung Woo ^[3]; Lee, Chong-Kil; Hwang, Bang Yeon; Han, Sang-Bae ^[1]; Kim, Youngsoo ^[1]

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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)

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.

• OSTI ID: 21032899
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 361; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CYSTEINE
IMMUNITY
INFLAMMATION
MACROPHAGES
PHOSPHORYLATION
PLANTS
RESIDUES