PMID:17185418

Citation	Carriere, V, Roussel, L, Ortega, N, Lacorre, DA, Americh, L, Aguilar, L, Bouche, G and Girard, JP (2007) IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc. Natl. Acad. Sci. U.S.A. 104:282-7
Abstract	Recent studies indicate that IL-1alpha functions intracellularly in pathways independent of its cell surface receptors by translocating to the nucleus and regulating transcription. Similarly, the chromatin-associated protein HMGB1 acts as both a nuclear factor and a secreted proinflammatory cytokine. Here, we show that IL-33, an IL-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines, is an endothelium-derived, chromatin-associated nuclear factor with transcriptional repressor properties. We found that IL-33 is identical to NF-HEV, a nuclear factor preferentially expressed in high endothelial venules (HEV), that we previously characterized. Accordingly, 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. Immunostaining with three distinct antisera, directed against the N-terminal part and IL-1-like C-terminal domain, revealed that IL-33 is a heterochromatin-associated nuclear factor in HEV endothelial cells in vivo. Association of IL-33 with heterochromatin was also observed in human and mouse cells under living conditions. In addition, colocalization of IL-33 with mitotic chromatin was noted. Nuclear localization, heterochromatin-association, and targeting to mitotic chromosomes were all found to be mediated by an evolutionarily conserved homeodomain-like helix-turn-helix motif within the IL-33 N-terminal part. Finally, IL-33 was found to possess transcriptional repressor properties, associated with the homeodomain-like helix-turn-helix motif. Together, these data suggest that, similarly to IL1alpha and HMGB1, IL-33 is a dual function protein that may function as both a proinflammatory cytokine and an intracellular nuclear factor with transcriptional regulatory properties.
Links	PubMed PMC1765450 Online version:10.1073/pnas.0606854104
Keywords	3T3 Cells; Amino Acid Motifs; Animals; Arthritis, Rheumatoid/metabolism; Conserved Sequence; Crohn Disease/metabolism; Endothelial Cells/metabolism; HeLa Cells; Heterochromatin/chemistry; Humans; Interleukin-33; Interleukins/chemistry; Interleukins/genetics; Interleukins/physiology; Membrane Proteins/physiology; Mice; Mitosis; Nuclear Localization Signals; Nuclear Proteins/physiology; RNA, Messenger/analysis; Receptors, Cell Surface/physiology; Receptors, Interleukin; Repressor Proteins/physiology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:IL33		GO:0045892: negative regulation of transcription, DNA-templated	ECO:0000315:		P		Figure 5 (A,B) show decrease in transcription	complete CACAO 11778
HUMAN:IL33		GO:0005720: nuclear heterochromatin	ECO:0000314:		C		Figure 2 (C,F,I) shows the association of IL33 expression with heterochromatin	complete CACAO 11779
HUMAN:IL33		GO:0000122: negative regulation of transcription from RNA polymerase II promoter	ECO:0000315:		P		Figure 5 (A,B) show decrease in transcription	complete CACAO 11832

References

See Help:References for how to manage references in GONUTS.