Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects.
Dennis M. de Graaf,Dennis M. de Graaf,Martin Jaeger,Inge C.L. van den Munckhof,Rob ter Horst,Kiki Schraa,Jelle Zwaag,Matthijs Kox,Mayumi Fujita,Takeshi Yamauchi,Laura Mercurio,Stefania Madonna,Joost H.W. Rutten,Jacqueline de Graaf,Niels P. Riksen,Frank L. van de Veerdonk,Mihai G. Netea,Leo A. B. Joosten,Charles A. Dinarello,Charles A. Dinarello +19 more
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It is concluded that a relative deficiency of the B cell product IL‐38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent withIL‐38 as an anti‐inflammatory cytokine.Abstract:
The IL-1 family member IL-38 (IL1F10) suppresses inflammatory and autoimmune conditions. Here, we report that plasma concentrations of IL-38 in 288 healthy Europeans correlate positively with circulating memory B cells and plasmablasts. IL-38 correlated negatively with age (p = 0.02) and was stable in 48 subjects for 1 year. In comparison with primary keratinocytes, IL1F10 expression in CD19(+) B cells from PBMC was lower, whereas cell-associated IL-38 expression was comparable. In vitro, IL-38 is released from CD19(+) B cells after stimulation with rituximab. Intravenous LPS in humans failed to induce circulating IL-38, compared to 100-fold induction of IL-6 and IL-1 receptor antagonist. In a cohort of 296 subjects with body mass index > 27 at high risk for cardiovascular disease, IL-38 plasma concentrations were significantly lower than in healthy subjects (p < 0.0001), and lowest in those with metabolic syndrome (p < 0.05). IL-38 also correlated inversely with high sensitivity C-reactive protein (p < 0.01), IL-6, IL-1Ra, and leptin (p < 0.05). We conclude that a relative deficiency of the B cell product IL-38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent with IL-38 as an anti-inflammatory cytokine.read more
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Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders.
TL;DR: In this article, the role and function of PI3K/AKT/mTOR molecular axis in the pathogenesis of different hyperproliferative skin disorders, including skin cancers, psoriasis, and atopic dermatitis (AD).
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IL-1 family cytokines as drivers and inhibitors of trained immunity
Lisa U. Teufel,Leo A. B. Joosten,Rob J.W. Arts,Mihai G. Netea,Charles A. Dinarello,Leo A. B. Joosten +5 more
TL;DR: In this article, the role of anti-inflammatory members of the IL-1 family of cytokines (IL-1F) which interfere with the inflammatory process has been discussed, with the potential to regulate the induction of a trained phenotype.
Journal ArticleDOI
IL-1 family cytokines as drivers and inhibitors of trained immunity
TL;DR: In this paper , the role of anti-inflammatory members of the IL-1 family of cytokines (IL-1F) which interfere with the inflammatory process has been discussed, with the potential to regulate the induction of a trained phenotype.
Journal ArticleDOI
IL-38 prevents induction of trained immunity by inhibition of mTOR signaling.
Dennis M. de Graaf,Dennis M. de Graaf,Lisa U. Teufel,Frank L. van de Veerdonk,Leo A. B. Joosten,Leo A. B. Joosten,Mihai G. Netea,Mihai G. Netea,Charles A. Dinarello,Charles A. Dinarello,Rob J. W. Arts,Rob J. W. Arts +11 more
TL;DR: This article showed that recombinant IL-38, an anti-inflammatory cytokine of the IL-1 family, was able to induce long-term inhibitory changes and reduce the induction of trained immunity by β-glucan in vivo in C57BL/6 mice and ex vivo in their bone marrow cells.
Journal ArticleDOI
IL-38 Ablation Reduces Local Inflammation and Disease Severity in Experimental Autoimmune Encephalomyelitis.
Arnaud Huard,Hoai Nam Do,Ann-Christin Frank,Evelyn Sirait-Fischer,Dominik C. Fuhrmann,Martine Catharina Josephine Hofmann,Rebecca Raue,Gaby Palmer,Bernhard Brüne,Bernhard Brüne,Natasja de Bruin,Andreas Weigert +11 more
TL;DR: In this paper, the role of IL-38 in experimental encephalomyelitis in mice was explored, which is, among others, driven by IL-17, and the IL-1 family receptor antagonist showed an alternative cell-intrinsic role in promoting inflammation in the CNS.
References
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Increasing Levels of Interleukin (IL)-1Ra and IL-6 During the First 2 Days of Hospitalization in Unstable Angina Are Associated With Increased Risk of In-Hospital Coronary Events
Luigi M. Biasucci,Giovanna Liuzzo,Giamila Fantuzzi,Giuseppina Caligiuri,Antonio Giuseppe Rebuzzi,Francesca Ginnetti,Charles A. Dinarello,Attilio Maseri +7 more
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Meta-analysis of genome-wide association studies in >80,000 subjects identifies multiple loci for C-reactive protein levels
Abbas Dehghan,Josée Dupuis,Josée Dupuis,Maja Barbalić,Joshua C. Bis,Gudny Eiriksdottir,Chen Lu,Niina Pellikka,Henri Wallaschofski,Johannes Kettunen,Peter Henneman,Jens Baumert,David P. Strachan,Christian Fuchsberger,Veronique Vitart,James F. Wilson,Guillaume Paré,Silvia Naitza,Megan E. Rudock,Ida Surakka,Eco J. C. de Geus,Behrooz Z. Alizadeh,Jack M. Guralnik,Alan R. Shuldiner,Toshiko Tanaka,Robert Y.L. Zee,Renate B. Schnabel,Vijay Nambi,Maryam Kavousi,Samuli Ripatti,Matthias Nauck,Nicholas L. Smith,Albert V. Smith,Jouko Sundvall,Paul Scheet,Yongmei Liu,Aimo Ruokonen,Lynda M. Rose,Martin G. Larson,Martin G. Larson,Ron C. Hoogeveen,Nelson B. Freimer,Alexander Teumer,Russell P. Tracy,Lenore J. Launer,Julie E. Buring,Jennifer F. Yamamoto,Jennifer F. Yamamoto,Aaron R. Folsom,Eric J.G. Sijbrands,James S. Pankow,Paul Elliott,John F. Keaney,John F. Keaney,Wei Sun,Antti-Pekka Sarin,João D. Fontes,João D. Fontes,Sunita Badola,Brad C. Astor,Albert Hofman,Anneli Pouta,Karl Werdan,Karin Halina Greiser,Karin Halina Greiser,Oliver Kuss,Henriette E. Meyer zu Schwabedissen,Joachim Thiery,Yalda Jamshidi,Yalda Jamshidi,Ilja M. Nolte,Nicole Soranzo,Tim D. Spector,Henry Völzke,Alex Parker,Thor Aspelund,David W. Bates,Lauren Young,Kim Tsui,David S. Siscovick,Xiuqing Guo,Jerome I. Rotter,Manuela Uda,David Schlessinger,Igor Rudan,Igor Rudan,Andrew A. Hicks,Brenda W.J.H. Penninx,Barbara Thorand,Christian Gieger,Joe Coresh,Gonneke Willemsen,Tamara B. Harris,André G. Uitterlinden,Marjo-Riitta Järvelin,Kenneth Rice,Dörte Radke,Veikko Salomaa,Ko Willems van Dijk,Eric Boerwinkle,Ramachandran S. Vasan,Luigi Ferrucci,Quince Gibson,Stefania Bandinelli,Harold Snieder,Dorret I. Boomsma,Xiangjun Xiao,Harry Campbell,Caroline Hayward,Peter P. Pramstaller,Cornelia M. van Duijn,Leena Peltonen,Bruce M. Psaty,Vilmundur Gudnason,Paul M. Ridker,Georg Homuth,Wolfgang Koenig,Christie M. Ballantyne,Jacqueline C.M. Witteman,Emelia J. Benjamin,Markus Perola,Daniel I. Chasman +121 more
TL;DR: A genome-wide association analysis of CRP identified 18 loci that were associated with CRP levels and highlighted immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.
Meta-Analysis of Genome-Wide Association Studies in > 80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels
Abbas Dehghan,Josée Dupuis,Maja Barbalić,Joshua C. Bis,Gudny Eiriksdottir,Chen Lu,Niina Pellikka,Henri Wallaschofski,Johannes Kettunen,Peter Henneman,Jens Baumert,David P. Strachan,Christian Fuchsberger,Veronique Vitart,James F. Wilson,Guillaume Paré,Silvia Naitza,Megan E. Rudock,Ida Surakka,Eco J. C. de Geus,Behrooz Z. Alizadeh,Jack M. Guralnik,Alan R. Shuldiner,Toshiko Tanaka,Robert Y.L. Zee,Renate B. Schnabel,Vijay Nambi,Maryam Kavousi,Samuli Ripatti,Matthias Nauck,Nicholas L. Smith,Albert V. Smith,Jouko Sundvall,Paul Scheet,Yongmei Liu,Aimo Ruokonen,Lynda M. Rose,Martin G. Larson,Ron C. Hoogeveen,Nelson B. Freimer,Alexander Teumer,Russell P. Tracy,Lenore J. Launer,Julie E. Buring,Jennifer F. Yamamoto,Aaron R. Folsom,Eric J.G. Sijbrands,James S. Pankow,Paul Elliott,John F. Keaney,Wei Sun,Antti-Pekka Sarin,João D. Fontes,Sunita Badola,Brad C. Astor,Albert Hofman,Anneli Pouta,Karl Werdan,Karin Halina Greiser,Oliver Kuss,Henriette E. Meyer zu Schwabedissen,Joachim Thiery,Yalda Jamshidi,Ilja M. Nolte,Nicole Soranzo,Tim D. Spector,Henry Voelzke,Alex Parker,Thor Aspelund,David W. Bates,Lauren Young,Kim Tsui,David S. Siscovick,Xiuqing Guo,Jerome I. Rotter,Manuela Uda,David Schlessinger,Igor Rudan,Andrew A. Hicks,Brenda W.J.H. Penninx,Barbara Thorand,Christian Gieger,Joe Coresh,Gonneke Willemsen,Tamara B. Harris,André G. Uitterlinden,Marjo-Riitta Järvelin,Kenneth Rice,Doerte Radke,Veikko Salomaa,Ko Willems van Dijk,Eric Boerwinkle,Ramachandran S. Vasan,Luigi Ferrucci,Quince Gibson,Stefania Bandinelli,Harold Snieder,Dorret I. Boomsma,Xiangjun Xiao,Harry Campbell,Caroline Hayward,Peter P. Pramstaller,Cornelia M. van Duijn,Leena Peltonen,Bruce M. Psaty,Vilmundur Gudnason,Paul M. Ridker,Georg Homuth,Wolfgang Koenig,Christie M. Ballantyne,Jacqueline C.M. Witteman,Emelia J. Benjamin,Markus Perola,Daniel I. Chasman +113 more