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CRTH2 receptor

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https://www.readbyqxmd.com/read/29867934/exposure-of-intestinal-epithelial-cells-to-short-and-long-chain-fructo-oligosaccharides-and-cpg-oligodeoxynucleotides-enhances-peanut-specific-t-helper-1-polarization
#1
Simone M Hayen, Henny G Otten, Saskia A Overbeek, André C Knulst, Johan Garssen, Linette E M Willemsen
Background: Non-digestible oligosaccharides promote colonization of beneficial gut bacteria and have direct immunomodulatory effects. Apical exposure of intestinal epithelial cells (IECs) to short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) in a transwell co-culture model enhanced the CpG-induced (TLR-9 ligand) T helper 1 (Th1) phenotype and regulatory IL-10 response of underlying peripheral mononuclear cells (PBMCs) of healthy donors. scGOS is derived from lactose and may pose risks in severe cow's milk allergic patients, and scFOS/lcFOS may be an alternative...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29848886/association-of-the-polymorphisms-in-th2-chemotaxis-related-genes-with-the-development-and-prognosis-of-autoimmune-thyroid-diseases
#2
Naoki Omori, Mikio Watanabe, Naoya Inoue, Junpei Taniguchi, Yoh Hidaka, Yoshinori Iwatani
The prognosis of autoimmune thyroid disease (AITD) is difficult to predict. Th2 cells suppress the differentiation of Th1 and Th17 cells, which are associated with the prognosis of AITD. However, there are few reports as to whether Th2 chemotaxis-related genes, such as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), IL-25, TARC/CCL17 (Thymus and activation regulated chemokine/chemokine ligand 17) or STAT6 (Signal transducer and activator of transcription 6), affect the pathology of and/or susceptibility to AITD...
May 30, 2018: Endocrine Journal
https://www.readbyqxmd.com/read/29765200/efficacy-and-safety-of-the-crth2-antagonist-azd1981-as-add-on-therapy-to-inhaled-corticosteroids-and-long-acting-%C3%AE-2-agonists-in-patients-with-atopic-asthma
#3
Eric D Bateman, Christopher O'Brien, Paul Rugman, Sally Luke, Stefan Ivanov, Mohib Uddin
Objectives: To evaluate the efficacy and safety of AZD1981, a potent, specific antagonist of the CRTh2 receptor, as add-on therapy to inhaled corticosteroids (ICS) and long-acting β2 -agonists (LABA), in patients with persistent asthma with an allergic component. Patients and methods: In this placebo-controlled, parallel-group Phase IIb study, patients with persistent atopic asthma on ICS and LABA were randomized to receive 12 weeks of treatment with placebo or AZD1981 (80 mg daily, 200 mg daily, and 10 mg, 40 mg, 100 mg, or 400 mg twice daily [BID])...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29743346/pgd2-dp2-receptor-activation-promotes-severe-viral-bronchiolitis-by-suppressing-ifn-%C3%AE-production
#4
Rhiannon B Werder, Jason P Lynch, Jennifer C Simpson, Vivian Zhang, Nick H Hodge, Matthew Poh, Elizabeth Forbes-Blom, Christina Kulis, Mark L Smythe, John W Upham, Kirsten Spann, Mark L Everard, Simon Phipps
Prostaglandin D2 (PGD2) signals through PGD2 receptor 2 (DP2, also known as CRTH2) on type 2 effector cells to promote asthma pathogenesis; however, little is known about its role during respiratory syncytial virus (RSV) bronchiolitis, a major risk factor for asthma development. We show that RSV infection up-regulated hematopoietic prostaglandin D synthase expression and increased PGD2 release by cultured human primary airway epithelial cells (AECs). Moreover, PGD2 production was elevated in nasopharyngeal samples from young infants hospitalized with RSV bronchiolitis compared to healthy controls...
May 9, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29678990/chemoattractant-receptor-homologous-molecule-expressed-on-th2-cells-crth2-antagonists-in-asthma-a-systematic-review-and-meta-analysis-protocol
#5
Wei Liu, Jie Min, Hongli Jiang, Bing Mao
INTRODUCTION: More than 20 orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists have moved forward to clinical development in recent years for the treatment of asthma. However, evidence from individual randomised controlled trials (RCTs) has demonstrated inconsistent results in their efficacy and safety. METHODS AND ANALYSIS: PubMed/Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, Global Index Medicus, Cochrane Central Register of Controlled Trials and Scopus will be searched from inception to 30 December 2017 for eligible RCTs, with additional studies being identified by manual searches...
April 20, 2018: BMJ Open
https://www.readbyqxmd.com/read/29607536/dp1-receptor-signaling-prevents-the-onset-of-intrinsic-apoptosis-in-eosinophils-and-functions-as-a-transcriptional-modulator
#6
Miriam Peinhaupt, David Roula, Anna Theiler, Miriam Sedej, Rudolf Schicho, Gunther Marsche, Eva M Sturm, Ian Sabroe, Marc E Rothenberg, Akos Heinemann
Prostaglandin (PG) D2 is the ligand for the G-protein coupled receptors DP1 (D-type prostanoid receptor 1) and DP2 (also known as chemoattractant receptor homologous molecule, expressed on Th2 cells; CRTH2). Both, DP1 and DP2 are expressed on the cellular surface of eosinophils; although it has become quite clear that PGD2 induces eosinophil migration mainly via DP2 receptors, the role of DP1 in eosinophil responses has remained elusive. In this study, we addressed how DP1 receptor signaling complements the pro-inflammatory effects of DP2...
April 1, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29454096/jak-stat-inhibitors-and-other-small-molecule-cytokine-antagonists-for-the-treatment-of-allergic-disease
#7
REVIEW
Michael D Howell, Carolyn Fitzsimons, Paul A Smith
OBJECTIVE: To provide an overview of janus kinase (JAK), chemoattractant receptor homologous molecule expressed on TH 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their use in the treatment of atopic dermatitis (AD), asthma, and allergic rhinitis (AR)...
April 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29427987/advances-and-evolving-concepts-in-allergic-asthma
#8
Hui-Ying Tung, Evan Li, Cameron Landers, An Nguyen, Farrah Kheradmand, J Morgan Knight, David B Corry
Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis...
February 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29363343/fevipiprant-in-the-treatment-of-asthma
#9
REVIEW
Christobelle White, Adam Wright, Christopher Brightling
Asthma is common and in many, particularly those with more severe disease, there remains a substantial unmet need. Success with biologics targeting eosinophilic inflammation underscore the value of treating inflammation in asthma beyond corticosteroids. Fevipiprant (QAW039) is an oral treatment for asthma. It competitively and reversibly antagonises the prostaglandin D2 receptor 2 (DP2) expressed on inflammatory and structural cells. Areas covered: We reviewed fevipiprant's mode of action and efficacy against other current and emerging pharmacological interventions for moderate-to-severe asthma...
February 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29335338/crth2-promotes-endoplasmic-reticulum-stress-induced-cardiomyocyte-apoptosis-through-m-calpain
#10
Shengkai Zuo, Deping Kong, Chenyao Wang, Jiao Liu, Yuanyang Wang, Qiangyou Wan, Shuai Yan, Jian Zhang, Juan Tang, Qianqian Zhang, Luheng Lyu, Xin Li, Zhixin Shan, Li Qian, Yujun Shen, Ying Yu
Apoptotic death of cardiac myocytes is associated with ischemic heart disease and chemotherapy-induced cardiomyopathy. Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) is highly expressed in the heart. However, its specific role in ischemic cardiomyopathy is not fully understood. Here, we demonstrated that CRTH2 disruption markedly improved cardiac recovery in mice postmyocardial infarction and doxorubicin challenge by suppressing cardiomyocyte apoptosis. Mechanistically, CRTH2 activation specifically facilitated endoplasmic reticulum (ER) stress-induced cardiomyocyte apoptosis via caspase-12-dependent pathway...
January 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29276415/crth2-antagonists-in-asthma-current-perspectives
#11
REVIEW
Dave Singh, Arjun Ravi, Thomas Southworth
Chemoattractant receptor-homologous molecule expressed on TH 2 cells (CRTH2) binds to prostaglandin D2 . CRTH2 is expressed on various cell types including eosinophils, mast cells, and basophils. CRTH2 and prostaglandin D2 are involved in allergic inflammation and eosinophil activation. Orally administered CRTH2 antagonists are in clinical development for the treatment of asthma. The biology and clinical trial data indicate that CRTH2 antagonists should be targeted toward eosinophilic asthma. This article reviews the clinical evidence for CRTH2 involvement in asthma pathophysiology and clinical trials of CRTH2 antagonists in asthma...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29110986/the-synthesis-of-2-3-6-trisubstituted-1-oxo-1-2-dihydroisoquinolines-as-potent-crth-2-antagonists
#12
Xianhai Huang, Ashwin Rao, Wei Zhou, Robert Aslanian, Ravi Nargund, Alexei Buevich, Li-Kang Zhang, Hongchen Qiu, Xiaoxin Yang, Charles G Garlisi, Craig Correll, Anandan Palani
New synthetic methods were developed for the preparation of 2,3,6-trisubstituted 1-oxo-1,2-dihydroisoquinolines as CRTh2 antagonists. The isoquinolinone core could be constructed before the introduction of substitution groups or synthesized through a catalytic intramolecular cyclization reaction with desired substitution groups properly installed. These synthetic strategies have helped to accelerate the SAR development of this series, and potent lead compounds were identified in both the CRTh2 receptor binding assay and the CD11b biomarker assay...
December 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28964637/neuroendocrine-cells-derived-chemokine-vasoactive-intestinal-polypeptide-vip-in-allergic-diseases
#13
REVIEW
Alok K Verma, Murli Manohar, Sathisha Upparahalli Venkateshaiah, Anil Mishra
Worldwide increase incidences of allergic diseases have heightened the interest of clinicians and researchers to understand the role of neuroendocrine cells in the recruitment and activation of inflammatory cells. Several pieces of evidence revealed the association of neuropeptides in the pathogenesis of allergic diseases. Importantly, one such peptide that is secreted by neuronal cells and immune cells exerts a wide spectrum of immunological functions as cytokine/chemokine is termed as Vasoactive Intestinal Peptide (VIP)...
December 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28888244/new-and-anticipated-therapies-for-severe-asthma
#14
REVIEW
Stephen P Peters, William W Busse
Asthma is frequently undertreated, resulting in a relatively high prevalence of patients with uncontrolled disease, characterized by the presence of symptoms and risk of adverse outcomes. Patients with uncontrolled asthma have a higher risk of morbidity and mortality, underscoring the importance of identifying uncontrolled disease and modifying management plans to improve control. Several assessment tools exist to evaluate control with various cutoff points and measures, but these tools do not reliably correlate with physiological measures and should be considered a supplement to physiological tests...
September 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28838980/fevipiprant-an-oral-prostaglandin-dp2-receptor-crth2-antagonist-in-allergic-asthma-uncontrolled-on-low-dose-inhaled-corticosteroids
#15
Eric D Bateman, Alfredo G Guerreros, Florian Brockhaus, Björn Holzhauer, Abhijit Pethe, Richard A Kay, Robert G Townley
Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d) or twice-daily (2, 25, 75 or 150 mg b.i.d) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.dFevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28818625/the-therapeutic-potential-of-crth2-dp2-beyond-allergy-and-asthma
#16
REVIEW
Katharina Jandl, Akos Heinemann
Prostaglandin (PG) D2 has been in the focus of research for quite a long time, but its biological effects and its roles in human disease are still not fully characterized. When in 2001 a second major PGD2 receptor termed chemoattractant receptor homologue expressed on Th2 cells (CRTH2; alternative name DP2) was discovered, diverse investigations started to shed more light on the complex and often controversial actions of the prostaglandin. With various immunomodulating effects, such as induction of migration, activation, and cytokine release of leukocytes observed both in vivo and in vitro, CRTH2 has emerged as a promising target for the treatment of allergic diseases...
November 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28679671/breast-regression-protein-39-chitinase-3-like-1-promotes-renal-fibrosis-after-kidney-injury-via-activation-of-myofibroblasts
#17
Tinika A Montgomery, Leyuan Xu, Sherene Mason, Amirtha Chinnadurai, Chun Geun Lee, Jack A Elias, Lloyd G Cantley
The normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein-39 (BRP-39), also known as chitinase 3-like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α 2 (IL13R α 2)-mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI...
November 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28669561/effects-of-icariin-on-asthma-mouse-model-are-associated-with-regulation-of-prostaglandin-d2-level
#18
J Qiao, S Sun, L Yuan, J Wang
BACKGROUND: We aimed to observe the effect of icariin on an asthma mouse model and explore the potential underlying mechanisms. METHODS: The asthma mouse model was established by ovalbumin (OVA) sensitisation and respiratory syncytial virus (RSV) infection and then treated with icariin. Airway resistance was assessed by whole body plethysmograph. In addition, pathological slides were stained with haematoxylin-eosin, and the peribronchial inflammation was observed microscopically...
June 29, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/28623133/prostaglandin-d-2-enhances-lipid-accumulation-through-suppression-of-lipolysis-via-dp2-crth2-receptors-in-adipocytes
#19
Eri Wakai, Kosuke Aritake, Yoshihiro Urade, Ko Fujimori
Prostaglandin (PG) D2 enhanced lipid accumulation in adipocytes. However, its molecular mechanism remains unclear. In this study, we investigated the regulatory mechanisms of PGD2 -elevated lipid accumulation in mouse adipocytic 3T3-L1 cells. The Gi-coupled DP2 (CRTH2) receptors (DP2R), one of the two-types of PGD2 receptors were dominantly expressed in adipocytes. A DP2R antagonist, CAY10595, but not DP1 receptor antagonist, BWA868C cleared the PGD2 -elevated intracellular triglyceride level. While, a DP2R agonist, 15R-15-methyl PGD2 (15R) increased the mRNA levels of the adipogenic and lipogenic genes, and decreased the glycerol release level...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28615072/chemokine-receptor-co-expression-reveals-aberrantly-distributed-t-h-effector-memory-cells-in-gpa-patients
#20
Lucas L Lintermans, Abraham Rutgers, Coen A Stegeman, Peter Heeringa, Wayel H Abdulahad
BACKGROUND: Persistent expansion of circulating CD4+ effector memory T cells (TEM ) in patients with granulomatosis with polyangiitis (GPA) suggests their fundamental role in disease pathogenesis. Recent studies have shown that distinct functional CD4+ TEM cell subsets can be identified based on expression patterns of chemokine receptors. The current study aimed to determine different CD4+ TEM cell subsets based on chemokine receptor expression in peripheral blood of GPA patients. Identification of particular circulating CD4+ TEM cells subsets may reveal distinct contributions of specific CD4+ TEM subsets to the disease pathogenesis in GPA...
June 14, 2017: Arthritis Research & Therapy
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