The dual function cytokine IL-33 interacts with the transcription factor NF-κB to dampen NF-κB-stimulated gene transcription.
J Immunol
; 187(4): 1609-16, 2011 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-21734074
ABSTRACT
Full-length IL-33 is a member of the IL-1 family of cytokines, which can act in an autocrine or paracrine manner by binding to the IL-33R on several different target cell types. In addition, IL-33 can act in an intracrine fashion by translocating to the nucleus, where it binds to the chromatin and modulates gene expression. In this article, we report that full-length IL-33, but not mature IL-33, interacts with the transcription factor NF-κB. This interaction occurs between the N-terminal part of IL-33 from aa 66-109 and the N-terminal Rel homology domain of NF-κB p65. Coimmunoprecipitation experiments in cells overexpressing IL-33 or endogenously expressing IL-33 revealed rhIL-1ß-stimulated association between IL-33 and p65, whereas binding to the p50 subunit was constitutive. The biological consequence of IL-33/NF-κB complex formation was reduction in NF-κB p65 binding to its cognate DNA and impairment of p65-triggered transactivation. Overexpression of IL-33 resulted in a reduction and delay in the rhIL-1ß-stimulated expression of endogenous NF-κB target genes such as IκBα, TNF-α, and C-REL. We suggest that nuclear IL-33 sequesters nuclear NF-κB and reduces NF-κB-triggered gene expression to dampen proinflammatory signaling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
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Interleukins
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NF-kappa B p50 Subunit
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Transcription Factor RelA
Limits:
Animals
/
Humans
Language:
En
Journal:
J Immunol
Year:
2011
Document type:
Article