Journal article

Authors list: Ali, S; Mohs, A; Thomas, M; Klare, J; Ross, R; Schmitz, ML; Martin, MU

Publication year: 2011

Pages: 1609-1616

Journal: The Journal of Immunology

Volume number: 187

Issue number: 4

ISSN: 0022-1767

DOI Link: https://doi.org/10.4049/jimmunol.1003080

Publisher: American Association of Immunologists

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-kappa B. This interaction occurs between the N-terminal part of IL-33 from aa 66-109 and the N-terminal Rel homology domain of NF-kappa B p65. Coimmunoprecipitation experiments in cells overexpressing IL-33 or endogenously expressing IL-33 revealed rhIL-1 beta-stimulated association between IL-33 and p65, whereas binding to the p50 subunit was constitutive. The biological consequence of IL-33/NF-kappa B complex formation was reduction in NF-kappa B 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-1 beta-stimulated expression of endogenous NF-kappa B target genes such as I kappa B alpha, TNF-alpha, and C-REL. We suggest that nuclear IL-33 sequesters nuclear NF-kappa B and reduces NF-kappa B-triggered gene expression to dampen proinflammatory signaling. The Journal of Immunology, 2011, 187: 1609-1616.

Harvard Citation style: Ali, S., Mohs, A., Thomas, M., Klare, J., Ross, R., Schmitz, M., et al. (2011) The Dual Function Cytokine IL-33 Interacts with the Transcription Factor NF-kappa B To Dampen NF-kappa B-Stimulated Gene Transcription, The Journal of Immunology, 187(4), pp. 1609-1616. https://doi.org/10.4049/jimmunol.1003080

APA Citation style: Ali, S., Mohs, A., Thomas, M., Klare, J., Ross, R., Schmitz, M., & Martin, M. (2011). The Dual Function Cytokine IL-33 Interacts with the Transcription Factor NF-kappa B To Dampen NF-kappa B-Stimulated Gene Transcription. The Journal of Immunology. 187(4), 1609-1616. https://doi.org/10.4049/jimmunol.1003080