Chemoprotection by phenolic antioxidants. Inhibition of tumor necrosis factor alpha induction in macrophages.
J Biol Chem
; 277(4): 2477-84, 2002 Jan 25.
Article
en En
| MEDLINE
| ID: mdl-11694529
ABSTRACT
Phenolic antioxidants exhibit anti-inflammatory activity in protection against chemical toxicity and cancer. To investigate the molecular mechanism of anti-inflammation, we analyzed the regulation of tumor necrosis factor alpha (TNF-alpha) expression in macrophages, a key step in inflammation, by the antioxidants. Whereas lipopolysaccharide (LPS), an inflammatory inducer, stimulates rapid synthesis of TNF-alpha protein, phenolic antioxidants, exemplified by tert-butyl hydroquinone and 1,4-dihydroquinone, block LPS-induced production of TNF-alpha protein in a time- and dose-dependent manner. Inhibition of TNF-alpha induction correlates with the capacity of the antioxidants to undergo oxidation-reduction cycling, implicating oxidative signaling in the inhibition. The antioxidants blocked LPS-induced increase of the steady-state mRNA of TNF-alpha but did not affect the half-life of the mRNA. Electrophoretic mobility shift assay reveals a total inhibition of LPS-induced formation of nuclear factor kappaB.DNA binding complexes by phenolic antioxidants. Finally, 1,4-dihydroquinone blocks the induction of TNF-alpha target genes interleukin 1beta and interleukin 6 at both mRNA and protein levels. Our findings demonstrate that phenolic antioxidants potently inhibit signal-induced TNF-alpha transcription and suggest a mechanism of anti-inflammation by the antioxidants through control of cytokine induction during inflammation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Necrosis Tumoral alfa
/
Fenol
/
Macrófagos
/
Antioxidantes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos