Honokiol suppresses TNF-α-induced neutrophil adhesion on cerebral endothelial cells by disrupting polyubiquitination and degradation of IκBα View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09

AUTHORS

Po-Jen Chen, Yu-Ling Wang, Liang-Mou Kuo, Chwan-Fwu Lin, Chun-Yu Chen, Yung-Fong Tsai, Jiann-Jong Shen, Tsong-Long Hwang

ABSTRACT

Adhesion molecules expressed on cerebral endothelial cells (ECs) mediate leukocyte recruitment and play a significant role in cerebral inflammation. Increased levels of adhesion molecules on the EC surface induce leukocyte infiltration into inflammatory areas and are thus hallmarkers of inflammation. Honokiol, isolated from the Chinese medicinal herb Magnolia officinalis, has various pharmacological activities, including anti-inflammatory effects, yet the nature of honokiol targeting molecules remains to be revealed. Here, we investigated the inhibitory effect of honokiol on neutrophil adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression, which underlie its molecular target, and mechanisms for inactivating nuclear factor κ enhancer binding protein (NF-κB) in mouse cerebral ECs. Honokiol inhibited tumour necrosis factor-α (TNF-α)-induced neutrophil adhesion and VCAM-1 gene expression in cerebral ECs. The inflammatory transcription factor NF-κB was downregulated by honokiol. Honokiol significantly blocked TNF-α-induced NF-κB p65 nuclear translocation and degradation of the proteasome-dependent inhibitor of NF-κB α (IκBα). From docking model prediction, honokiol directly targeted the ubiquitin-ubiquitin interface of Lys48-linked polychains. Moreover, honokiol prevented the TNF-α-induced Lys48-linked polyubiquitination, including IκBα-polyubiquitin interaction. Honokiol has protective anti-inflammatory effects on TNF-α-induced neutrophil adhesion and VCAM-1 gene expression in cerebral ECs, at least in part by directly inhibiting ubiquitination-mediated IκBα degradation and then preventing NF-κB nuclear translocation. More... »

PAGES

26554

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep26554

DOI

http://dx.doi.org/10.1038/srep26554

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023573222

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27212040


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