Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling.
Détails
ID Serval
serval:BIB_FB03A6E6C71B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling.
Périodique
Journal of Clinical Investigation
Collaborateur⸱rice⸱s
CARDIoGRAM Consortium, CHARGE Inflammation Working Group, CHARGE Heart Failure Working Group
Contributeur⸱rice⸱s
Kathiresan S., Reilly MP., Samani NJ., Schunkert H., Erdmann J., Assimes TL., Boerwinkle E., Erdmann J., Hall A., Hengstenberg C., Kathiresan S., König IR., Laaksonen R., McPherson R., Reilly MP., Samani NJ., Schunkert H., Thompson JR., Thorsteinsdottir U., Ziegler A., König IR., Thompson JR., Absher D., Chen L., Cupples LA., Halperin E., Li M., Musunuru K., Preuss M., Schillert A., Thorleifsson G., Voight BF., Wells GA., Absher D., Assimes TL., Fortmann S., Go A., Hlatky M., Iribarren C., Knowles J., Myers R., Quertermous T., Sidney S., Risch N., Tang H., Blankenberg S., Zeller T., Schillert A., Wild P., Ziegler A., Schnabel R., Sinning C., Lackner K., Tiret L., Nicaud V., Cambien F., Bickel C., Rupprecht HJ., Perret C., Proust C., Münzel T., Barbalic M., Bis J., Boerwinkle E., Chen IY., Cupples LA., Dehghan A., Demissie-Banjaw S., Folsom A., Glazer N., Gudnason V., Harris T., Heckbert S., Levy D., Lumley T., Marciante K., Morrison A., O'Donnell CJ., Psaty BM., Rice K., Rotter JI., Siscovick DS., Smith N., Smith A., Taylor KD., van Duijn C., Volcik K., Whitteman J., Ramachandran V., Hofman A., Uitterlinden A., Gretarsdottir S., Gulcher JR., Holm H., Kong A., Stefansson K., Thorgeirsson G., Andersen K., Thorleifsson G., Thorsteinsdottir U., Erdmann J., Fischer M., Grosshennig A., Hengstenberg C., König IR., Lieb W., Linsel-Nitschke P., Preuss M., Stark K., Schreiber S., Wichmann HE., Ziegler A., Schunkert H., Aherrahrou Z., Bruse P., Doering A., Erdmann J., Hengstenberg C., Illig T., Klopp N., König IR., Diemert P., Loley C., Medack A., Meisinger C., Meitinger T., Nahrstedt J., Peters A., Preuss M., Stark K., Wagner AK., Wichmann HE., Willenborg C., Ziegler A., Schunkert H., Böhm BO., Dobnig H., Grammer TB., Halperin E., Hoffmann MM., Kleber M., Laaksonen R., März W., Meinitzer A., Winkelmann BR., Pilz S., Renner W., Scharnagl H., Stojakovic T., Tomaschitz A., Winkler K., Voight BF., Musunuru K., Guiducci C., Burtt N., Gabriel SB., Siscovick DS., O'Donnell CJ., Elosua R., Peltonen L., Salomaa V., Schwartz SM., Melander O., Altshuler D., Kathiresan S., Stewart AF., Chen L., Dandona S., Wells GA., Jarinova O., McPherson R., Roberts R., Reilly MP., Li M., Qu L., Wilensky R., Matthai W., Hakonarson HH., Devaney J., Burnett MS., Pichard AD., Kent KM., Satler L., Lindsay JM., Waksman R., Knouff CW., Waterworth DM., Walker MC., Mooser V., Epstein SE., Rader DJ., Samani NJ., Thompson JR., Braund PS., Nelson CP., Wright BJ., Balmforth AJ., Ball SG., Hall AS.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
123
Numéro
10
Pages
4208-4218
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
The suppression of tumorigenicity 2/IL-33 (ST2/IL-33) pathway has been implicated in several immune and inflammatory diseases. ST2 is produced as 2 isoforms. The membrane-bound isoform (ST2L) induces an immune response when bound to its ligand, IL-33. The other isoform is a soluble protein (sST2) that is thought to be a decoy receptor for IL-33 signaling. Elevated sST2 levels in serum are associated with an increased risk for cardiovascular disease. We investigated the determinants of sST2 plasma concentrations in 2,991 Framingham Offspring Cohort participants. While clinical and environmental factors explained some variation in sST2 levels, much of the variation in sST2 production was driven by genetic factors. In a genome-wide association study (GWAS), multiple SNPs within IL1RL1 (the gene encoding ST2) demonstrated associations with sST2 concentrations. Five missense variants of IL1RL1 correlated with higher sST2 levels in the GWAS and mapped to the intracellular domain of ST2, which is absent in sST2. In a cell culture model, IL1RL1 missense variants increased sST2 expression by inducing IL-33 expression and enhancing IL-33 responsiveness (via ST2L). Our data suggest that genetic variation in IL1RL1 can result in increased levels of sST2 and alter immune and inflammatory signaling through the ST2/IL-33 pathway.
Mots-clé
Amino Acid Substitution, Female, Gene Expression, Gene Expression Regulation, Genetic Association Studies, HEK293 Cells, Humans, Interleukins/genetics, Interleukins/metabolism, Male, Middle Aged, Models, Molecular, Myelin and Lymphocyte-Associated Proteolipid Proteins/metabolism, Myeloid Differentiation Factor 88/metabolism, NF-kappa B/metabolism, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Prospective Studies, Protein Structure, Tertiary, Receptors, Cell Surface/chemistry, Receptors, Cell Surface/genetics, Signal Transduction, Transcription Factor AP-1/metabolism
Pubmed
Open Access
Oui
Création de la notice
10/10/2014 11:44
Dernière modification de la notice
20/08/2019 17:26
Données d'usage
