The Dual Function Cytokine IL-33 Interacts with the Transcription Factor NF-κB To Dampen NF-κB–Stimulated Gene Transcription

  title={The Dual Function Cytokine IL-33 Interacts with the Transcription Factor NF-$\kappa$B To Dampen NF-$\kappa$B–Stimulated Gene Transcription},
  author={Shafaqat Ali and Antje Mohs and Meike Thomas and Jan Klare and Ralf Ross and Michael Lienhard Schmitz and Michael U. Martin},
  journal={The Journal of Immunology},
  pages={1609 - 1616}
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… 

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The results indicate that IL-33 has a role in inflammatory skin diseases, in which IFN-γ and TNF-α are present in high levels.

The Deubiquitinase USP17 Regulates the Stability and Nuclear Function of IL-33

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Deubiquitination and stabilization of IL-33 by USP21.

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Regulation of IL-33 Expression by IFN-c and Tumor Necrosis Factor-a in Normal Human Epidermal

The results indicate that IL-33 has a role in inflammatory skin diseases, in which IFN-g and TNF-a are present in high levels.

The alarmin IL-33 is a notch target in quiescent endothelial cells.




IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo

In situ hybridization demonstrated that endothelial cells constitute a major source of IL-33 mRNA in chronically inflamed tissues from patients with rheumatoid arthritis and Crohn's disease, and data suggest thatIL-33 is a dual function protein that may function as both a proinflammatory cytokine and an intracellular nuclear factor with transcriptional regulatory properties.

The IL-1-Like Cytokine IL-33 Is Constitutively Expressed in the Nucleus of Endothelial Cells and Epithelial Cells In Vivo: A Novel ‘Alarmin’?

It is speculated that IL-33 may function, similarly to the prototype ‘alarmin’ HMGB1, as an endogenous ‘danger’ signal to alert the immune system after endothelial or epithelial cell damage during trauma or infection.

IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells

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The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1

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Recombination signal sequence binding protein Jkappa is constitutively bound to the NF-kappaB site of the interleukin-6 promoter and acts as a negative regulatory factor

Binding analysis suggests that the amount of RBP-Jkappa protein present in the nucleus is severalfold higher than the total amount of inducible NF-kappaB complexes but that the latter bind DNA with a 10-fold-higher affinity, suggesting that such a mechanism could be involved in the constitutive repression of the IL-6 gene under normal physiological conditions.

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