TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes.
Nat Immunol
; 9(4): 378-87, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18345002
ABSTRACT
Rapid induction of inflammatory genes by tumor necrosis factor (TNF) has been well studied, but little is known about delayed and chronic TNF responses. Here we investigated the kinetics of primary macrophage responses to TNF and discovered that TNF initiates an interferon-beta-mediated autocrine loop that sustains expression of inflammatory genes and induces delayed expression of interferon-response genes such as those encoding the transcription factors STAT1 and IRF7, which enhance macrophage responses to stimulation of cytokines and Toll-like receptors. TNF-induced interferon-beta production depended on interferon-response factor 1, and downstream gene expression was mediated by synergy between small amounts of interferon-beta and canonical TNF-induced signals. Thus, TNF activates a 'feed-forward' loop that sustains inflammation but avoids the potential toxicity associated with the high interferon production induced by stimulation of Toll-like receptors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interferon Tipo I
/
Regulação da Expressão Gênica
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Fator de Necrose Tumoral alfa
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Quimiocinas
/
Comunicação Autócrina
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Fator de Transcrição STAT1
/
Fator Regulador 1 de Interferon
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos