Tags

Type your tag names separated by a space and hit enter

Magnolol suppresses NF-kappaB activation and NF-kappaB regulated gene expression through inhibition of IkappaB kinase activation.
Mol Immunol. 2007 Apr; 44(10):2647-58.MI

Abstract

The mis-regulation of nuclear factor-kappa B (NF-kappaB) signal pathway is involved in a variety of inflammatory diseases that leds to the production of inflammatory mediators. Our studies using human U937 promonocytes cells suggested that magnolol, a low molecular weight lignan isolated from the medicinal plant Magnolia officinalis, differentially down-regulated the pharmacologically induced expression of NF-kappaB-regulated inflammatory gene products MMP-9, IL-8, MCP-1, MIP-1alpha, TNF-alpha. Pre-treatment of magnolol blocked TNF-alpha-induced NF-kappaB activation in different cell types as evidenced by EMSA. Magnolol did not directly affect the binding of p65/p50 heterodimer to DNA. Immunoblot analysis demonstrated that magnolol inhibited the TNF-alpha-stimulated phosphorylation and degradation of the cytosolic NF-kappaB inhibitor IkappaBalpha and the effects were dose-dependent. Mechanistically, a non-radioactive IkappaB kinases (IKK) assay using immunoprecipitated IKKs protein demonstrated that magnolol inhibited both intrinsic and TNF-alpha-stimulated IKK activity, thus suggesting a critical role of magnolol in abrogating the phosphorylation and degradation of IkappaBalpha. The involvement of IKK was further verified in a HeLa cell NF-kappaB-dependent luciferase reporter system. In this system magnolol suppressed luciferase expression stimulated by TNF-alpha and by the transient transfection and expression of NIK (NF-kappaB-inducing kinase), wild type IKKbeta, constitutively active IKKalpha and IKKbeta, or the p65 subunit. Magnolol was also found to inhibit the nuclear translocation and phosphorylation of p65 subunit of NF-kappaB. In line with the observation that NF-kappaB activation may up-regulate anti-apoptotic genes, it was shown in U937 cells that magnolol enhanced TNF-alpha-induced apoptotic cell death. Our results suggest that magnolol or its derivatives may have potential anti-inflammatory actions through IKK inactivation.

Authors+Show Affiliations

Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Hong Kong SAR, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17240450

Citation

Tse, Anfernee Kai-Wing, et al. "Magnolol Suppresses NF-kappaB Activation and NF-kappaB Regulated Gene Expression Through Inhibition of IkappaB Kinase Activation." Molecular Immunology, vol. 44, no. 10, 2007, pp. 2647-58.
Tse AK, Wan CK, Zhu GY, et al. Magnolol suppresses NF-kappaB activation and NF-kappaB regulated gene expression through inhibition of IkappaB kinase activation. Mol Immunol. 2007;44(10):2647-58.
Tse, A. K., Wan, C. K., Zhu, G. Y., Shen, X. L., Cheung, H. Y., Yang, M., & Fong, W. F. (2007). Magnolol suppresses NF-kappaB activation and NF-kappaB regulated gene expression through inhibition of IkappaB kinase activation. Molecular Immunology, 44(10), 2647-58.
Tse AK, et al. Magnolol Suppresses NF-kappaB Activation and NF-kappaB Regulated Gene Expression Through Inhibition of IkappaB Kinase Activation. Mol Immunol. 2007;44(10):2647-58. PubMed PMID: 17240450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Magnolol suppresses NF-kappaB activation and NF-kappaB regulated gene expression through inhibition of IkappaB kinase activation. AU - Tse,Anfernee Kai-Wing, AU - Wan,Chi-Keung, AU - Zhu,Guo-Yuan, AU - Shen,Xiao-Ling, AU - Cheung,Hon-Yeung, AU - Yang,Mengsu, AU - Fong,Wang-Fun, Y1 - 2007/01/22/ PY - 2006/11/14/received PY - 2006/12/10/accepted PY - 2007/1/24/pubmed PY - 2007/6/2/medline PY - 2007/1/24/entrez SP - 2647 EP - 58 JF - Molecular immunology JO - Mol Immunol VL - 44 IS - 10 N2 - The mis-regulation of nuclear factor-kappa B (NF-kappaB) signal pathway is involved in a variety of inflammatory diseases that leds to the production of inflammatory mediators. Our studies using human U937 promonocytes cells suggested that magnolol, a low molecular weight lignan isolated from the medicinal plant Magnolia officinalis, differentially down-regulated the pharmacologically induced expression of NF-kappaB-regulated inflammatory gene products MMP-9, IL-8, MCP-1, MIP-1alpha, TNF-alpha. Pre-treatment of magnolol blocked TNF-alpha-induced NF-kappaB activation in different cell types as evidenced by EMSA. Magnolol did not directly affect the binding of p65/p50 heterodimer to DNA. Immunoblot analysis demonstrated that magnolol inhibited the TNF-alpha-stimulated phosphorylation and degradation of the cytosolic NF-kappaB inhibitor IkappaBalpha and the effects were dose-dependent. Mechanistically, a non-radioactive IkappaB kinases (IKK) assay using immunoprecipitated IKKs protein demonstrated that magnolol inhibited both intrinsic and TNF-alpha-stimulated IKK activity, thus suggesting a critical role of magnolol in abrogating the phosphorylation and degradation of IkappaBalpha. The involvement of IKK was further verified in a HeLa cell NF-kappaB-dependent luciferase reporter system. In this system magnolol suppressed luciferase expression stimulated by TNF-alpha and by the transient transfection and expression of NIK (NF-kappaB-inducing kinase), wild type IKKbeta, constitutively active IKKalpha and IKKbeta, or the p65 subunit. Magnolol was also found to inhibit the nuclear translocation and phosphorylation of p65 subunit of NF-kappaB. In line with the observation that NF-kappaB activation may up-regulate anti-apoptotic genes, it was shown in U937 cells that magnolol enhanced TNF-alpha-induced apoptotic cell death. Our results suggest that magnolol or its derivatives may have potential anti-inflammatory actions through IKK inactivation. SN - 0161-5890 UR - https://www.unboundmedicine.com/medline/citation/17240450/Magnolol_suppresses_NF_kappaB_activation_and_NF_kappaB_regulated_gene_expression_through_inhibition_of_IkappaB_kinase_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(06)00727-9 DB - PRIME DP - Unbound Medicine ER -