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Moritz F Eissmann, Christine Dijkstra, Merridee A Wouters, David Baloyan, Dmitri Mouradov, Paul M Nguyen, Mercedes Davalos-Salas, Tracy L Putoczki, Oliver M Sieber, John M Mariadason, Matthias Ernst, Frederick Masson
Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts of IL33 and its receptor St2. IL33 is therefore continuously released during homeostatic turnover of the intestinal mucosa. Although IL33 can prevent colon cancer associated with inflammatory colitis, the contribution of IL33 signaling to sporadic colon cancer remains unknown. Here, we utilized a mouse model of sporadic colon cancer to investigate the contribution of IL33 signaling to tumorigenesis in the absence of pre-existing inflammation...
February 20, 2018: Cancer Immunology Research
Franka Klatte-Schulz, Susann Minkwitz, Aysha Schmock, Nicole Bormann, Alper Kurtoglu, Serafeim Tsitsilonis, Sebastian Manegold, Britt Wildemann
Reasons for the development of chronic tendon pathologies are still under debate and more basic knowledge is needed about the different diseases. The aim of the present study was therefore to characterize different acute and chronic Achilles tendon disorders. Achilles tendon samples from patients with chronic tendinopathy (n = 7), chronic ruptures (n = 6), acute ruptures (n = 13), and intact tendons (n = 4) were analyzed. The histological score investigating pathological changes was significantly increased in tendinopathy and chronic ruptures compared to acute ruptures...
January 30, 2018: International Journal of Molecular Sciences
Corinne Cayrol, Jean-Philippe Girard
Interleukin-33 (IL-33) is a tissue-derived nuclear cytokine from the IL-1 family abundantly expressed in endothelial cells, epithelial cells and fibroblast-like cells, both during homeostasis and inflammation. It functions as an alarm signal (alarmin) released upon cell injury or tissue damage to alert immune cells expressing the ST2 receptor (IL-1RL1). The major targets of IL-33 in vivo are tissue-resident immune cells such as mast cells, group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs)...
January 2018: Immunological Reviews
Mukesh Verma, Sucai Liu, Lidia Michalec, Anand Sripada, Magdalena M Gorska, Rafeul Alam
BACKGROUND: IL-33 plays an important role in the development of experimental asthma. OBJECTIVE: We sought to study the role of the IL-33 receptor suppressor of tumorigenicity 2 (ST2) in the persistence of asthma in a mouse model. METHODS: We studied allergen-induced experimental asthma in ST2 knockout (KO) and wild-type control mice. We measured airway hyperresponsiveness by using flexiVent; inflammatory indices by using ELISA, histology, and real-time PCR; and type 2 innate lymphoid cells (ILC2s) in lung single-cell preparations by using flow cytometry...
November 10, 2017: Journal of Allergy and Clinical Immunology
David Díaz-Jiménez, Lucía Núñez, Marjorie De la Fuente, Karen Dubois-Camacho, Hugo Sepúlveda, Martín Montecino, Alejandro Torres-Riquelme, Paulina García-González, Jonás Chnaiderman, Anna Vossenkamper, Thomas T MacDonald, Daniela Simian, María-Julieta González, John A Cidlowski, Rodrigo Quera, Marcela A Hermoso
The ST2/IL33 signalling pathway has been associated with ulcerative colitis (UC). ST2, encoded by the IL1RL1 gene, is expressed as both a membrane-anchored receptor (ST2L) activated by IL33 and as a soluble receptor (sST2) with anti-inflammatory properties. In UC patients, sST2 is further increased by corticosteroid treatment; however, the glucocorticoid-mediated molecular regulation remains unknown. We therefore tested whether genetic variants in the IL1RL1 distal promoter are involved in UC and affect glucocorticoid-mediated ST2 expression...
August 31, 2017: Scientific Reports
Dirk Smith, Hannes Helgason, Patrick Sulem, Unnur Steina Bjornsdottir, Ai Ching Lim, Gardar Sveinbjornsson, Haruki Hasegawa, Michael Brown, Randal R Ketchem, Monica Gavala, Logan Garrett, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Olafur T Magnusson, Gudmundur I Eyjolfsson, Isleifur Olafsson, Pall Torfi Onundarson, Olof Sigurdardottir, David Gislason, Thorarinn Gislason, Bjorn Runar Ludviksson, Dora Ludviksdottir, H Marike Boezen, Andrea Heinzmann, Marcus Krueger, Celeste Porsbjerg, Tarunveer S Ahluwalia, Johannes Waage, Vibeke Backer, Klaus A Deichmann, Gerard H Koppelman, Klaus Bønnelykke, Hans Bisgaard, Gisli Masson, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, James A Johnston, Ingileif Jonsdottir, Kari Stefansson
IL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon...
March 2017: PLoS Genetics
G A Queiroz, R S Costa, N M Alcantara-Neves, G Nunes de Oliveira Costa, M L Barreto, V L Carneiro, C A Figueiredo
Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13). Interleukin-33 (IL-33) appears to be a potent inducer of Th2 immune response. This occurs when IL-33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation...
April 2017: International Journal of Immunogenetics
Claire Galand, Juan Manuel Leyva-Castillo, Juhan Yoon, Alex Han, Margaret S Lee, Andrew N J McKenzie, Michael Stassen, Michiko K Oyoshi, Fred D Finkelman, Raif S Geha
BACKGROUND: Cutaneous exposure to food allergens predisposes to food allergy, which is commonly associated with atopic dermatitis (AD). Levels of the epithelial cytokine IL-33 are increased in skin lesions and serum of patients with AD. Mast cells (MCs) play a critical role in food-induced anaphylaxis and express the IL-33 receptor ST2. The role of IL-33 in patients with MC-dependent food anaphylaxis is unknown. OBJECTIVE: We sought to determine the role and mechanism of action of IL-33 in patients with food-induced anaphylaxis in a model of IgE-dependent food anaphylaxis elicited by oral challenge of epicutaneously sensitized mice...
November 2016: Journal of Allergy and Clinical Immunology
Gregory Noel, Muhammad Imran Arshad, Aveline Filliol, Valentine Genet, Michel Rauch, Catherine Lucas-Clerc, Agnès Lehuen, Jean-Philippe Girard, Claire Piquet-Pellorce, Michel Samson
The IL-33/ST2 axis plays a protective role in T-cell-mediated hepatitis, but little is known about the functional impact of endogenous IL-33 on liver immunopathology. We used IL-33-deficient mice to investigate the functional effect of endogenous IL-33 in concanavalin A (Con A)-hepatitis. IL-33(-/-) mice displayed more severe Con A liver injury than wild-type (WT) mice, consistent with a hepatoprotective effect of IL-33. The more severe hepatic injury in IL-33(-/-) mice was associated with significantly higher levels of TNF-α and IL-1β and a larger number of NK cells infiltrating the liver...
August 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Andrea Marzullo, Francesca Ambrosi, Mirjam Inchingolo, Fabio Manca, Fiorella Devito, Domenico Angiletta, Annapaola Zito, Pietro Scicchitano, Marco Matteo Ciccone
BACKGROUND: ST2 (suppression of tumorigenity) has been described as a receptor for the interleukin-33, a member of the IL-1 family of cytokines. It is associated to coronary artery disease, all-causes mortality and cardiovascular mortality. AIMS: The present study was designed to assess the immunohistochemical expression of the ST2 receptor (ST2L/Il-1R) in atherosclerotic plaques of formalin fixed paraffin-embedded internal carotid arteries of patients with and without cerebro-vascular symptoms...
2016: PloS One
D P E Margiotta, L Navarini, M Vadacca, M Lo Vullo, F Pignataro, F Basta, A Afeltra
OBJECTIVE: Primary Sjogren's Syndrome (pSS) is a systemic autoimmune disorder characterized by infiltration of the exocrine glands leading to secretory insufficiency. Despite the progress made in understanding the pathogenesis of the SS, many aspects remain to be clarified. Interleukin-33 (IL33) is a recently discovered cytokine, belonging to IL-1 superfamily. IL33 and its soluble receptor ST2 were implied in a number of immune and in autoimmune diseases pathogenesis. In this work ,we analyzed expression of IL33 and ST2 in Sjogren's syndrome...
April 2016: European Review for Medical and Pharmacological Sciences
Wei-Yu Chen, Ya-Jen Chang, Chia-Hao Su, Tzu-Hsien Tsai, Shang-Der Chen, Chung-Hsi Hsing, Jenq-Lin Yang
Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneys using RNA sequencing (RNAseq)...
May 13, 2016: Biochemical and Biophysical Research Communications
Rui Li, Gang Yang, Ruiqi Yang, Xiaoxing Peng, Jing Li
IL33/ST2 axis activates airway eosinophils that exacerbate airway inflammation. The data was obtained from PubMed, EMBASE, Clinical trial, Cochrane Library, Web of science, CNKI and Wanfang database with time restrictions of 1 Jan, 2000 to 15 Feb, 2016. The meta-analysis was performed using Review Manager 5.2 software. After searching, total 15 documents were included into this meta-analysis, involving in 633 asthma patients and 379 healthy people. The meta-analysis results revealed that the serum IL33 or ST2 level was higher in asthma patients compared to that in healthy people...
2015: International Journal of Clinical and Experimental Medicine
X Wang, Y F Zhu, D M Li, Q Qin, Q Wang, F S Muhali, W J Jiang, J A Zhang
Interleukin 33 (IL33) / ST2 pathway and ST2-interlukin18 receptor1-interlukin18 receptor accessory protein (ST2-IL18R1-IL18RAP) gene cluster have been involved in many autoimmune diseases but few report in autoimmune thyroid diseases (AITD). In this study, we investigated whether polymorphisms of IL33, ST2, IL18R1, and IL18RAP are associated with Graves' disease (GD) and Hashimoto's thyroiditis (HT), two major forms of AITD, among a Chinese population. A total of 11 SNPs were explored in a case-control study including 417 patients with GD, 250 HT patients and 301 controls, including rs1929992, rs10975519, rs10208293, rs6543116, rs1041973, rs3732127, rs11465597, rs1035130, rs2293225, rs1035127, rs917997 of IL 33, ST2-IL18R1-IL18RAP gene cluster...
February 2016: International Journal of Immunogenetics
David M Ansell, Matthew J Hardman
No abstract text is available yet for this article.
January 2016: Experimental Dermatology
Farnaz Zahedi Avval, Shadi Shomali, Mohammad Nadri, Reza Boostani, Lida Jarahi, Masoud Youssefi
ST2 is a member of IL-1 receptor family expressed on Th2 cells and regulates Th2 responces. The gene of ST2 encodes soluble ST2 (sST2) and the transmembrane ST2 (ST2L) isoforms through alternative mRNA splicing. The discovery of IL33/ ST2 signaling pathway, has drawn a great scientific attention to this system. sST2 has been shown to be an indacating factor in various infl ammatory conditions. This study aims to evaluate serum sST2 levels in HTLV-1 infected patients. This study included 49 HTLV-1 seropositive cases of which 14 were sympthomatic...
June 2015: Acta Microbiologica et Immunologica Hungarica
Wei-Yu Chen, Jaewoo Hong, Joseph Gannon, Rahul Kakkar, Richard T Lee
Hypertension increases the pressure load on the heart and is associated with a poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33) binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy receptor for IL-33, blocking myocardial and vascular benefits, and is a prognostic biomarker in patients with cardiovascular diseases. Here we report that a highly local intramyocardial IL-33/ST2 conversation regulates the heart's response to pressure overload...
June 9, 2015: Proceedings of the National Academy of Sciences of the United States of America
Dawn K Reichenbach, Vincent Schwarze, Benjamin M Matta, Victor Tkachev, Elisabeth Lieberknecht, Quan Liu, Brent H Koehn, Dietmar Pfeifer, Patricia A Taylor, Gabriele Prinz, Heide Dierbach, Natalie Stickel, Yvonne Beck, Max Warncke, Tobias Junt, Annette Schmitt-Graeff, Susumu Nakae, Marie Follo, Tobias Wertheimer, Lukas Schwab, Jason Devlin, Simon C Watkins, Justus Duyster, James L M Ferrara, Heth R Turnquist, Robert Zeiser, Bruce R Blazar
Interleukin (IL)-33 binding to the receptor suppression of tumorigenicity 2 (ST2) produces pro-inflammatory and anti-inflammatory effects. Increased levels of soluble ST2 (sST2) are a biomarker for steroid-refractory graft-versus-host disease (GVHD) and mortality. However, whether sST2 has a role as an immune modulator or only as a biomarker during GVHD was unclear. We show increased IL-33 production by nonhematopoietic cells in the gastrointestinal (GI) tract in mice post-conditioning and patients during GVHD...
May 14, 2015: Blood
J Malcolm, R A Awang, J Oliver-Bell, J P Butcher, L Campbell, A Adrados Planell, D F Lappin, S Y Fukada, C J Nile, F Y Liew, S Culshaw
Cytokines mediate the balance between protective and destructive immunity in periodontitis. We sought to investigate the role of IL-33 in periodontitis. The expression of IL-33 in gingival tissue from healthy controls (n = 10) and patients with chronic periodontitis (n = 17) was investigated. Based on a murine model of periodontal disease, the function of IL-33 was determined first by administration of exogenous IL-33 and second by inhibition of IL-33 signaling using mice deficient in the IL-33 receptor ST2...
July 2015: Journal of Dental Research
Jin-hua Yang, Fang-qin Wu, Qiang Wen, Wen-cai Zhang, Yang-e Wang, Xin Xiong, Yan-wen Su, Long-xian Cheng
This study investigated the relationship between IL-33/ST2 signal pathway gene polymorphisms and myocardial infarction (MI) in Han Chinese. A case-control association analysis was performed on a total of 490 MI patients (MI group) and 929 normal subjects (NC group). Sequenom Mass Array and Taqman genotyping technique were used to analyze the tag single nucleotide polymorphisms (SNPs) in the genes encoding IL-33, ST2, and IL-1RaP (rs11792633, rs1041973 and rs4624606). The results showed that the frequencies of rs4624606 genotypes AA, TT, AT were 0...
February 2015: Journal of Huazhong University of Science and Technology. Medical Sciences
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