IKIP Negatively Regulates NF-κB Activation and Inflammation through Inhibition of IKKα/ß Phosphorylation.
J Immunol
; 204(2): 418-427, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31826938
ABSTRACT
Stringent regulation of the transcription factor NF-κB signaling is essential for the activation of host immune responses and maintaining homeostasis, yet the molecular mechanisms involved in its tight regulation are not completely understood. In this study, we report that IKK-interacting protein (IKIP) negatively regulates NF-κB activation. IKIP interacted with IKKα/ß to block its association with NEMO, thereby inhibiting the phosphorylation of IKKα/ß and the activation of NF-κB. Upon LPS, TNF-α, and IL-1ß stimulation, IKIP-deficient macrophages exhibited more and prolonged IKKα/ß phosphorylation, IκB, and p65 phosphorylation and production of NF-κB-responsive genes. Moreover, IKIP-deficient mice were more susceptible to LPS-induced septic shock and dextran sodium sulfate-induced colitis. Our study identifies a previously unrecognized role for IKIP in the negative regulation of NF-κB activation by inhibition of IKKα/ß phosphorylation through the disruption of IKK complex formation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colite
/
Quinase I-kappa B
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Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article