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Titre du document / Document title

Suppression of iNOS expression by fucoidan is mediated by regulation of p38 MAPK, JAK/STAT, AP-1 and IRF-1, and depends on up-regulation of scavenger receptor B1 expression in TNF-α- and IFN-γ-stimulated C6 glioma cells

Auteur(s) / Author(s)

HANG DO (1) ; SUHKNEUNG PYO (1) ; SOHN Eun-Hwa (2) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Division of Immunopharmacology, College of Pharmacy, Sungkyunkwan University, Kyunggi-do 440-746, COREE, REPUBLIQUE DE
(2) Department of Herbal Medicine Resource, Institute of Bioscience and Biotechnology, Kangwon National University, Gangwon-do 245-711, COREE, REPUBLIQUE DE

Résumé / Abstract

In neurodegenerative disorders, activated glial cells overproduce nitric oxide (NO), which causes neurotoxicity. Inducible NO synthase (iNOS) is a potential therapeutic target in neurodegenerative diseases. Here, we examined the action of fucoidan, a high-molecular-weight sulfated polysaccharide, on tumor necrosis factor-α (TNF-α)- and interferon-γ (IFN-γ)-induced NO production in C6 glioma cells. Fucoidan suppressed TNF-α- and IFN-γ-induced NO production and iNOS expression. In addition, fucoidan inhibited TNF-α- and IFN-γ-induced AP-1, IRF-1, JAK/STAT and p38 mitogen-activated protein kinase (MAPK) activation and induced scavenger receptor B1 (SR-B1) expression. Blocking of sR-B1 did not reverse the inhibitory effect of fucoidan on TNF-α- and IFN-γ- stimulated NO production. However, inhibition of sR-B1 expression by siRNA increased iNOS expression and p38 phosphorylation in TNF-α- and IFN-γ-stimulated C6 cells. Overall, p38 MAPK, AP-1, JAK/STAT and IRF-1 play an important role in the inhibitory effect of fucoidan on TNF-α- and IFN-γ-stimulated NO production, and intracellular SR-B1 expression may be related to the inhibition of iNOS expression by fucoidan via regulation of p38 phosphorylation. The present results also suggest that fucoidan could be a potential therapeutic agent for treating inflammatory-related neuronal injury in neurological disorders.

Revue / Journal Title

Journal of nutritional biochemistry    ISSN  0955-2863 

Source / Source

2010, vol. 21, no8, pp. 671-679 [9 page(s) (article)] (42 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, New York, NY, ETATS-UNIS  (1990) (Revue)

Mots-clés anglais / English Keywords

Cytokine

;

Vertebrata

;

Enzyme

;

Transferases

;

AP1 transcription factor

;

Mammalia

;

Neuroglia

;

In vitro

;

Cell line

;

Glial cell

;

Gamma interferon

;

Tumor necrosis factor α

;

Biological receptor

;

Mitogen-activated protein kinase

;

Regulation(control)

;

Gene expression

;

Mots-clés français / French Keywords

Cytokine

;

Vertebrata

;

Enzyme

;

Transferases

;

Facteur transcription AP1

;

Lignée C6

;

Mammalia

;

Névroglie

;

In vitro

;

Lignée cellulaire

;

Cellule gliale

;

Interféron gamma

;

Facteur nécrose tumorale α

;

Récepteur biologique

;

Mitogen-activated protein kinase

;

Régulation

;

Expression génique

;

Mots-clés espagnols / Spanish Keywords

Citoquina

;

Vertebrata

;

Enzima

;

Transferases

;

Mammalia

;

Neuroglia

;

In vitro

;

Línea celular

;

Célula glial

;

Interferón gamma

;

Factor necrosis tumoral α

;

Receptor biológico

;

Mitogen-activated protein kinase

;

Regulación

;

Expresión genética

;

Mots-clés d'auteur / Author Keywords

Fucoidan

;

iNOS

;

p38

;

SRB1

;

Glia

;

Localisation / Location

INIST-CNRS, Cote INIST : 15374, 35400019177709.0020

Nº notice refdoc (ud4) : 23078616



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