IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo
Virginie Carriere,Lucie Roussel,Nathalie Ortega,Delphine-Armelle Lacorre,Laure Americh,Luc Aguilar,Gérard Bouche,Jean-Philippe Girard +7 more
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TLDR
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.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.read more
Citations
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Immunological and Inflammatory Functions of the Interleukin-1 Family
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TL;DR: The triggers and receptor pathways that result in sterile inflammation and its impact on human health are reviewed.
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Interleukin-1 in the pathogenesis and treatment of inflammatory diseases
TL;DR: This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL- 1 family of ligands and receptors.
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A large-scale, consortium-based genomewide association study of asthma.
Miriam F. Moffatt,Ivo Gut,Florence Demenais,David P. Strachan,Emmanuelle Bouzigon,Simon Heath,Erika von Mutius,Martin Farrall,Mark Lathrop,William O.C.M. Cookson +9 more
TL;DR: A few common alleles are associated with disease risk at all ages and suggest a role for communication of epithelial damage to the adaptive immune system and activation of airway inflammation in asthma.
Supplementary materials to a paper "A large-scale, consortium-based genomewide association study of asthma"
Moffatt Mf,Gut Ig,F. Demenais,Strachan Dp,E. Bouzigon,S. Heath,A. Kumar,P. Burney,D. Jarvis,M. Wjst,M. Kogevinas,R. Jogi,C. Janson,Franklin Ka,E. Omenaas,B. Leynaert,I. Pin,J. Heinrich,Probst Hensch Nm,Anto Jm,J. Sunyer,Maldonado Ja,J. Martinez Moratalla,I. Urrutia,F. Payo,F. Kauffmann,Dizier Mh,V. Siroux,A. Boznanski,C. Braun Fahrländer,J. Genuneit,J. Glas,E. Horak,M. Kabesch,Pillai Sg,Helms Pj,K. Carlsen,Carlsen Kh,J. Gerritsen,M. Silverman,P. Sly,J. Tsanakas,A. Von Berg,M. Whyte,M. Blumenthal,M. Imboden,T. Rochat,Thun Ga,Gerbase Mw,I. Curjuric,Gaspoz Jm,Liu Lj,Wouters Im,T. Sigsgaard,D. Heederik,I. Basinas,V. Schlunssen,Ø. Omland,P. Cullinan,R. Vermeulen,J. Henderson,R. Granell,McArdle Wl,Smith Gd,James Al,J. Hui,Palmer Lj,J. Beilby,Musk Aw,C. Laprise,Hudson Tj,M. Lemire,D. Daley,A. Becker,M. Chan Yeung,A. Sandford,Kozyrskyj Al,P. Paré,A. Ferguson,H. Dimich Ward,Watson Wt,Freidin Mb,Bragina EIu,Deev Ia,Deeva Ev,Kobyakova Os,Puzyrev Vp,Ogorodova Lm,Khusnutdinova Ek,Karunas As,Fedorova Yy,Hall Ip,I. Sayers,Tobin Md,Wan Yi,Heaney Lg,Al Momani Ba,Mansur Ah,S. Manney,Thomson Nc,R. Chaudhuri,Brightling Ce,M. Bafadhel,A. Singapuri,R. Niven,A. Simpson,Holloway Jw,Howarth Ph,Polonikov Av,Ivanov Vp,Solodilova Ma,E. Melén,G. Pershagen,A. Bergström,I. Kull,F. Nyberg,M. Wickman,C. Söderhäll,J. Kere,Postma Ds,M. Kerkhof,B. Brunekreef,Smit Ha,de Jongste Jc,A. Wijga,Aalberse Rc,Hoekstra Mo,Koppelman Gh,A. Binia,Chung Kf,P. Bhavsar,F. Chow,P. Macedo,A. Menzies Gow,N. van Stiphout,A. Bush,Lee Ya,J. Esparza Gordillo,R. Nickel,U. Wahn,S. Lau,I. Marenholz,T. Haahtela,L. von Hertzen,P. Jousilahti,T. Laatikainen,Mäkelä Mj,E. Vartiainen,T. Laitinen,Balding Dj,Peden Jf,E. Corda,D. Lechner,C. Besse,D. Zelenika,A. Boland,D. Bacq,S. Demonchy,H. Blanche,Y. Kamatani,E. von Mutius,M. Farrall,M. Lathrop,Cookson Wo +163 more
References
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Journal ArticleDOI
Biologic basis for interleukin-1 in disease
TL;DR: This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references, which summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.
Journal ArticleDOI
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
TL;DR: It is reported that Hmgb1-/- necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours, and cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.
Journal ArticleDOI
HMG-1 as a Late Mediator of Endotoxin Lethality in Mice
Haichao Wang,Ona Bloom,Minghuang Zhang,Jaideep M. Vishnubhakat,Michael Ombrellino,Jiantu Che,Asia Frazier,Huan Yang,Svetlana Ivanova,Lyudmila V. Borovikova,Kirk R. Manogue,Eugen Faist,Edward Abraham,Jan Andersson,Ulf Andersson,Patricia E. Molina,Naji N. Abumrad,Andrew E. Sama,Kevin J. Tracey +18 more
TL;DR: High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1, and showed increased serum levels after endotoxin exposure, suggesting that this protein warrants investigation as a therapeutic target.
Journal ArticleDOI
IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
Jochen Schmitz,Alexander Owyang,Elizabeth R. Oldham,Yaoli Song,Erin Murphy,Terril K. McClanahan,Gerard Zurawski,Mehrdad M. Moshrefi,Jinzhong Qin,Xiaoxia Li,Daniel M. Gorman,J. Fernando Bazan,Robert A. Kastelein +12 more
TL;DR: A member of theIL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T( H)2 cells is reported.
Journal ArticleDOI
High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal.
Michael T. Lotze,Kevin J. Tracey +1 more
TL;DR: These features of HMGB1 are discussed and recent advances that have led to the preclinical development of therapeutics that modulateHMGB1 release and activity are summarized.