| First Author | Ali S | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 4 | Pages | 1609-16 |
| PubMed ID | 21734074 | Mgi Jnum | J:179171 |
| Mgi Id | MGI:5301228 | Doi | 10.4049/jimmunol.1003080 |
| Citation | Ali S, et al. (2011) The dual function cytokine IL-33 interacts with the transcription factor NF-kappaB to dampen NF-kappaB-stimulated gene transcription. J Immunol 187(4):1609-16 |
| abstractText | 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-kappaB. This interaction occurs between the N-terminal part of IL-33 from aa 66-109 and the N-terminal Rel homology domain of NF-kappaB p65. Coimmunoprecipitation experiments in cells overexpressing IL-33 or endogenously expressing IL-33 revealed rhIL-1beta-stimulated association between IL-33 and p65, whereas binding to the p50 subunit was constitutive. The biological consequence of IL-33/NF-kappaB complex formation was reduction in NF-kappaB 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-1beta-stimulated expression of endogenous NF-kappaB target genes such as IkappaBalpha, TNF-alpha, and C-REL. We suggest that nuclear IL-33 sequesters nuclear NF-kappaB and reduces NF-kappaB-triggered gene expression to dampen proinflammatory signaling. |
