Inducible TAP1 Negatively Regulates the Antiviral Innate Immune Response by Targeting the TAK1 Complex.
J Immunol
; 198(9): 3690-3704, 2017 05 01.
Article
em En
| MEDLINE
| ID: mdl-28356387
ABSTRACT
The innate immune response is critical for host defense and must be tightly controlled, but the molecular mechanisms responsible for its negative regulation are not yet completely understood. In this study, we report that transporter 1, ATP-binding cassette, subfamily B (TAP1), a virus-inducible endoplasmic reticulum-associated protein, negatively regulated the virus-triggered immune response. In this study, we observed upregulated expression of TAP1 following virus infection in human lung epithelial cells (A549), THP-1 monocytes, HeLa cells, and Vero cells. The overexpression of TAP1 enhanced virus replication by inhibiting the virus-triggered activation of NF-κB signaling and the production of IFNs, IFN-stimulated genes, and proinflammatory cytokines. TAP1 depletion had the opposite effect. In response to virus infection, TAP1 interacted with the TGF-ß-activated kinase (TAK)1 complex and impaired the phosphorylation of TAK1, subsequently suppressing the phosphorylation of the IκB kinase complex and NF-κB inhibitor α (IκBα) as well as NF-κB nuclear translocation. Our findings collectively suggest that TAP1 plays a novel role in the negative regulation of virus-triggered NF-κB signaling and the innate immune response by targeting the TAK1 complex.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
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Mucosa Respiratória
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MAP Quinase Quinase Quinases
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Influenza Humana
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Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article