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IL-33 ST2

Monika Ryba-Stanisławowska, Paulina Werner, Maria Skrzypkowska, Agnieszka Brandt, Jolanta Myśliwska
IL-33 is an IL-1 cytokine family member, with ability to induce both Th1 and Th2 immune responses. It binds to ST2 receptor, whose deficiency is associated with enhanced inflammatory response. The most recent studies have shown the immunoregulatory effect of IL-33 on Tregs in animal models. As type 1 diabetes is an autoimmune, inflammatory disease, where Treg defects have been described, we aimed to analyze the in vitro influence of recombinant IL-33 on quantitative properties of regulatory CD4(+)CD25(high)FOXP3(+) T cells...
2016: Mediators of Inflammation
Jinggang Xia, Yang Qu, Chunlin Yin, Dong Xu
BACKGROUND: This study aimed to evaluate the role of β-blocker therapy on modulating interleukin (IL)-33/ST2 (interleukin-1 receptor-like 1) signaling during ventricular remodeling related to heart failure (HF) after acute myocardial infarction (AMI). METHODS: Sprague-Dawley rats that survived surgery to induce AMI were randomly divided into the placebo group and the β-blocker treatment group. A sham group was used as a control. Left ventricular (LV) function variables, the myocardial infarct size, fibrosis and IL-33/ST2 protein expression was measured...
October 17, 2016: Cardiology Journal
Sofia Theodoropoulou, David A Copland, Jian Liu, Jiahui Wu, Peter J Gardner, Ema Ozaki, Sarah L Doyle, Matthew Campbell, Andrew D Dick
Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. Loss of retinal pigment epithelium (RPE) is a major pathological hallmark in AMD with or without pathological neovascularization. Although activation of the immune system is implicated in disease progression, pathological pathways remain diverse and unclear. Here, we report an unexpected protective role of a pro-inflammatory cytokine, interleukin-33 (IL-33) in ocular angiogenesis. IL-33 and its receptor (ST2) are expressed constitutively in human and murine retina and choroid...
October 4, 2016: Journal of Pathology
Erin D Gordon, Joe Palandra, Agata Wesolowska-Andersen, Lando Ringel, Cydney L Rios, Marrah E Lachowicz-Scroggins, Louis Z Sharp, Jamie L Everman, Hannah J MacLeod, Jae W Lee, Robert J Mason, Michael A Matthay, Richard T Sheldon, Michael C Peters, Karl H Nocka, John V Fahy, Max A Seibold
Genome-wide association studies of asthma have identified genetic variants in the IL1RL1 gene, but the molecular mechanisms conferring risk are unknown. IL1RL1 encodes the ST2 receptor (ST2L) for IL-33 and an inhibitory decoy receptor (sST2). IL-33 promotes type 2 inflammation, which is present in some but not all asthmatics. We find that two single nucleotide polymorphisms (SNPs) in IL1RL1 - rs1420101 and rs11685480 - are strongly associated with plasma sST2 levels, though neither is an expression quantitative trait locus (eQTL) in whole blood...
September 8, 2016: JCI Insight
Ralf Willebrand, David Voehringer
Eosinophils are major effector cells during allergic responses and helminth infections. Recent studies further highlight eosinophils as important players in many other biological processes. Therefore it is important to understand how these cells can be modulated in terms of survival and effector function. In the present study we investigated how eosinophils respond to the alarmin IL-33. We show that IL-33 promotes eosinophil survival in a ST2- and MyD88-dependent manner. IL-33-mediated protection from apoptosis was dependent on autocrine GM-CSF release...
2016: PloS One
Laura K Johnston, Chia-Lin Hsu, Rebecca A Krier-Burris, Krishan D Chhiba, Karen B Chien, Andrew McKenzie, Sergejs Berdnikovs, Paul J Bryce
Eosinophils are important in the pathogenesis of many diseases, including asthma, eosinophilic esophagitis, and eczema. Whereas IL-5 is crucial for supporting mature eosinophils (EoMs), the signals that support earlier eosinophil lineage events are less defined. The IL-33R, ST2, is expressed on several inflammatory cells, including eosinophils, and is best characterized for its role during the initiation of allergic responses in peripheral tissues. Recently, ST2 expression was described on hematopoietic progenitor subsets, where its function remains controversial...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Mingyuan Han, Jun Young Hong, Suraj Jaipalli, Charu Rajput, Jing Lei, Joanna L Hinde, Qiang Chen, Natalie M Hershenson, J Kelley Bentley, Marc B Hershenson
Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of six day-old mice induces mucous metaplasia and airways hyperresponsiveness which is dependent on IL-13, IL-25 and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-γ expression, in contrast to mature 8 week-old mice with a robust IFN-γ response, consistent with the notion that deficient IFN-γ production in immature mice permits RV-induced type 2 immune responses...
September 28, 2016: American Journal of Respiratory Cell and Molecular Biology
Ayako Matsuki, Hiroaki Takatori, Sohei Makita, Masaya Yokota, Tomohiro Tamachi, Akira Suto, Kotaro Suzuki, Koichi Hirose, Hiroshi Nakajima
BACKGROUND: Innate lymphoid cells (ILCs) are emerging subsets of immune cells that produce large amounts of cytokines upon cytokine and/or alarmin stimulation. Recent studies have shown that T-bet plays pivotal roles in the development of ILC3s and ILC1s; however, the roles of T-bet in lung ILC2s remain unknown. OBJECTIVE: To determine the role of T-bet in ILC2-mediated airway inflammation. METHODS: The expression of T-bet in lung ILCs (defined as Thy1...
September 23, 2016: Journal of Allergy and Clinical Immunology
Chunhong Wang, Zengsheng Chen, Xiangmao Bu, Yang Han, Shan Shan, Tao Ren, Weiqing Song
IL-33 is a member of IL-1 superfamily that drives production of Th2-related cytokines. Recently, accumulating evidence suggest an involvement of IL-33 in carcinogenesis. Herein, we determine a close correlation of IL-33 expression and cancer progress in patients with non-small-cell lung cancer (NSCLC). Overexpression of IL-33 by transfection with IL-33 expression vector enhances NSCLC outgrowth and metastasis, while genetic knockdown of IL-33 by transfection with IL-33 shRNA limits NSCLC progression. In consistent, IL-33 stimulation of NSCLC cells leads to robust NSCLC outgrowth and metastasis in vitro and in vivo...
October 21, 2016: Biochemical and Biophysical Research Communications
Ronaldo A Ribeiro, Carlos W S Wanderley, Deysi V T Wong, José Maurício S C Mota, Caio A V G Leite, Marcellus H L P Souza, Fernando Q Cunha, Roberto C P Lima-Júnior
PURPOSE: Intestinal mucositis and diarrhea are common manifestations of anticancer regimens that include irinotecan, 5-fluorouracil (5-FU), and other cytotoxic drugs. These side effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy, resulting in dose reductions and treatment discontinuation. Here, we aimed to review the experimental evidence regarding possible new targets for the management of irinotecan- and 5-FU-related intestinal mucositis. METHODS: A literature search was performed using the PubMed and MEDLINE databases...
September 2, 2016: Cancer Chemotherapy and Pharmacology
Lihua Duan, Yan Huang, Qun Su, Qingyan Lin, Wen Liu, Jiao Luo, Bing Yu, Yan He, Hongyan Qian, Yuan Liu, Jie Chen, Guixiu Shi
Interleukin-33 (IL-33), the most recently discovered member of the IL-1 superfamily, has been linked to several human pathologies including autoimmune diseases, sepsis, and allergy through its specific IL-1 receptor ST2. However, there is little information regarding the role of IL-33 in gout. In this study, we investigated the potential role of IL-33 in gout patients. The serum level of IL-33 was measured by ELISA, and the clinical and laboratory parameters, serum creatinine, urea, and lipid, were extracted from medical record system...
2016: Journal of Diabetes Research
Rafiou Agoro, Julie Piotet-Morin, Jennifer Palomo, Chloé Michaudel, Solenne Vigne, Isabelle Maillet, Pauline Chenuet, Noëlline Guillou, Jessica Le Bérichel, Malgorzata Kisielow, Ulf Per Flodby, Marc Le Bert, Valérie Quesniaux, Matthias Muller, Franco Di Padova, Bernhard Ryffel, Cem Gabay, Aurélie Couturier-Maillard
Allergic asthma is characterized by a strong Th2 response with inflammatory cell recruitment and structural changes in the lung. Papain is a protease allergen disrupting the airway epithelium triggering a rapid inflammation with eosinophilia mediated by innate lymphoid cell activation (ILC2) and leading to a Th2 immune response. In this study, we focused on inflammatory responses to a single exposure to papain and showed that intranasal administration of papain results in the recruitment of inflammatory cells, including neutrophils and eosinophils with a rapid production of IL-1α, IL-1β, and IL-33...
August 28, 2016: European Journal of Immunology
David Díaz-Jiménez, Marjorie De la Fuente, Karen Dubois-Camacho, Glauben Landskron, Janitza Fuentes, Tamara Pérez, María Julieta González, Daniela Simian, Marcela A Hermoso, Rodrigo Quera
BACKGROUND: The ST2/IL-33 pathway has been related to ulcerative colitis (UC), and soluble ST2 (sST2), to disease severity. We tested the potential usefulness of sST2 as a predictive marker of treatment response and patients' outcome. METHODS: Twenty-six patients with active UC were prospectively recruited and grouped according to an endoscopic score and therapy response. Colonoscopic biopsies were collected at baseline and 6 months or when patients showed clinical activity...
2016: BMC Gastroenterology
Xiaoyu Zhao, Xiaojian Zhang, Ying Lv, Yuming Xu, Menglong Li, Qingxia Pan, Yaojuan Chu, Nan Liu, Guang-Xian Zhang, Lin Zhu
Interleukin (IL)-33 is a recently described member of the IL-1 family and functions as a ligand for ST2, a member of the IL-1 receptor family. The role of IL-33/ST2 axis in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS), remains controversial. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, the underlying immunoregulatory mechanisms have not been fully elucidated, and whether this effect of MAT is through inhibiting the function of the IL-33/ST2 axis is not known...
October 2016: Immunology Letters
Jiayun Shen, Qing Shang, Chun-Kwok Wong, Edmund K Li, Emily W Kun, Isaac T Cheng, Martin Li, Tena K Li, Tracy Y Zhu, Cheuk-Man Yu, Ling Qin, Lai-Shan Tam
Psoriatic arthritis (PsA) patients have increased risk of both atherosclerosis and osteoporosis. Previous studies revealed that IL-33/ST2 axis may be related to both conditions; however, these associations were never evaluated in a single patients' group. Here we explored the association among plasma levels of IL-33 and its decoy receptor soluble ST2 (sST2), carotid plaque determined by ultrasound, and volumetric bone mineral density (vBMD)/microstructure of distal radius measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 80 PsA patients (55% male; 53...
2016: Scientific Reports
Julia Siede, Anja Fröhlich, Angeliki Datsi, Ahmed N Hegazy, Domonkos V Varga, Vivien Holecska, Hirohisa Saito, Susumu Nakae, Max Löhning
Immunomodulatory Foxp3+ regulatory T cells (Tregs) form a heterogeneous population consisting of subsets with different activation states, migratory properties and suppressive functions. Recently, expression of the IL-33 receptor ST2 was shown on Tregs in inflammatory settings. Here we report that ST2 expression identifies highly activated Tregs in mice even under homeostatic conditions. ST2+ Tregs preferentially accumulate at non-lymphoid sites, likely mediated by their high expression of several chemokine receptors facilitating tissue homing...
2016: PloS One
Jing Chang, Yue-Feng Xia, Ma-Zhong Zhang, Li-Ming Zhang
Interleukin (IL)-33, a member of the IL-1 cytokine super-family, acts as both a traditional cytokine and an intracellular nuclear factor. It is generally released from damaged immune cells and signals through its receptor ST2 in an autocrine and paracrine fashion, plays important roles in type-2 innate immunity, and functions as an "alarmin" or a danger signal for cellular damage or cellular stress. Here, we review recent advances of the role of IL-33 in lung injury and explore its potential significance as an attractive therapeutic target...
2016: Translational Perioperative and Pain Medicine
Neal L Millar, Charlotte O'Donnell, Iain B McInnes, Elizabeth Brint
IL-33 is a member of the IL-1 family of cytokines. IL-33 is predominantly located within the nucleus of cells where it plays a role in gene regulation. Given the right combination of signals and cellular damage, stored IL-33 is released from the cell where it can interact with its receptor ST2, triggering danger-associated responses and act as a cellular "alarmin". Whilst IL-33/ST2 signalling has been shown to induce potent pro-inflammatory responses that can be detrimental in certain disease states, a dichotomous, protective role of IL-33 in promoting wound healing has also emerged in multiple tissues types...
August 10, 2016: Seminars in Cell & Developmental Biology
Shyamala Ganesan, Duc Pham, Yaxun Jing, Mohammad Farazuddin, Magdalena H Hudy, Benjamin Unger, Adam T Comstock, David Proud, Adam S Lauring, Uma S Sajjan
Airway epithelial cells are the major target for rhinovirus (RV) infection and express proinflammatory chemokines and antiviral cytokines that play a role in innate immunity. Previously, we demonstrated that RV interaction with TLR2 causes ILR-associated kinase-1 (IRAK-1) depletion in both airway epithelial cells and macrophages. Further, IRAK-1 degradation caused by TLR2 activation was shown to inhibit ssRNA-induced IFN expression in dendritic cells. Therefore, in this study, we examined the role of TLR2 and IRAK-1 in RV-induced IFN-β, IFN-λ1, and CXCL-10, which require signaling by viral RNA...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Joel Mathews, Nandini Krishnamoorthy, David Itiro Kasahara, Youngji Cho, Allison Patricia Wurmbrand, Luiza Ribeiro, Dirk Smith, Dale Umetsu, Bruce D Levy, Stephanie Ann Shore
BACKGROUND: Ozone increases IL-33 in the lungs, and obesity augments the pulmonary effects of acute ozone exposure. OBJECTIVES: To assess the role of IL-33 in the augmented effects of ozone observed in obese mice. METHODS: Lean wildtype and obese db/db mice were pretreated with antibodies blocking the IL-33 receptor, ST2, and then exposed to ozone (2 ppm for 3 h). Airway responsiveness was assessed, bronchoalveolar lavage (BAL) was performed, and lung cells harvested for flow cytometry 24 hours later...
July 29, 2016: Environmental Health Perspectives
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