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CRTH2 receptor

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https://www.readbyqxmd.com/read/28964637/neuroendocrine-cells-derived-chemokine-vasoactive-intestinal-polypeptide-vip-in-allergic-diseases
#1
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)...
September 23, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28888244/new-and-anticipated-therapies-for-severe-asthma
#2
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
#3
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
#4
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...
August 14, 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
#5
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 α2 (IL13Rα2)-mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI...
July 5, 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
#6
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-d2-enhances-lipid-accumulation-through-suppression-of-lipolysis-via-dp2-crth2-receptors-in-adipocytes
#7
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-th-effector-memory-cells-in-gpa-patients
#8
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...
June 14, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28612233/targeting-the-pgd2-crth2-dp1-signaling-pathway-in-asthma-and-allergic-disease-current-status-and-future-perspectives
#9
Maciej Kupczyk, Piotr Kuna
Prostaglandin D2 (PGD2) released by degranulating mast cells is believed to play a key role in orchestrating mechanisms of inflammation in allergies and asthma. The biological effects of PGD2 are mediated by D-prostanoid (DP1), CRTH2 (DP2), and thromboxane prostanoid (TP) receptors. The CRTH2 receptor is involved in induction of migration and activation of T helper type 2 (Th2) lymphocytes, eosinophils, and basophils; up-regulation of adhesion molecules; and promotion of pro-inflammatory Th2-type cytokines (interleukin [IL]-4, 5, 13), whereas the DP receptor is associated with relaxation of smooth muscles, vasodilation, inhibition of cell migration, and apoptosis of eosinophils...
August 2017: Drugs
https://www.readbyqxmd.com/read/28609567/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-the-novel-crth2-antagonist-bi-1021958-at-single-oral-doses-in-healthy-men-and-multiple-oral-doses-in-men-and-women-with-well-controlled-asthma
#10
Andy Fowler, Rüdiger Koenen, James Hilbert, Jon Blatchford, Dominik Kappeler, Ewald Benediktus, Chester Wood, Abhya Gupta
BI 1021958, a novel antagonist of the chemoattractant-receptor-homologous molecule (CRTH2), targets airway inflammation in asthma by inhibiting prostaglandin binding to CRTH2 receptors. Two phase 1 studies assessed BI 1021958 safety/tolerability and pharmacokinetics (PK)/pharmacodynamics (PD) following single doses in healthy men and multiple doses in men/women with well-controlled asthma. Studies 1 had 2 parts: a placebo-controlled, fixed-sequence, single-blind, single-rising-dose part (n = 56) and a randomized, 2-way crossover, open-label, repeated-dose part studying the food effect on PK/PD (n = 12)...
November 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28442499/absorption-distribution-metabolism-and-excretion-of-the-oral-prostaglandin-d2-receptor-2-dp2-antagonist-fevipiprant-qaw039-in-healthy-volunteers-and-in-vitro
#11
David Pearson, H Markus Weiss, Yi Jin, Jan Jaap van Lier, Veit J Erpenbeck, Ulrike Glaenzel, Peter End, Ralph Woessner, Fabian Eggimann, Gian Camenisch
Fevipiprant is a novel oral prostaglandin D2 receptor 2 (DP2; also known as CRTh2) antagonist, which is currently in development for the treatment of severe asthma and atopic dermatitis. We investigated the absorption, distribution, metabolism, and excretion properties of fevipiprant in healthy subjects after a single 200 mg oral dose of [(14)C]-radiolabeled fevipiprant. Fevipiprant and metabolites were analyzed by liquid chromatography coupled to tandem mass spectrometry and radioactivity measurements, and mechanistic in vitro studies were performed to investigate clearance pathways and covalent plasma protein binding...
April 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28394950/generation-and-characterization-of-an-antagonistic-monoclonal-antibody-against-an-extracellular-domain-of-mouse-dp2-crth2-gpr44-receptors-for-prostaglandin-d2
#12
Nanae Nagata, Hiroko Iwanari, Hidetoshi Kumagai, Osamu Kusano-Arai, Yuichi Ikeda, Kosuke Aritake, Takao Hamakubo, Yoshihiro Urade
Prostaglandin D2 (PGD2) is a lipid mediator involved in sleep regulation and inflammation. PGD2 interacts with 2 types of G protein-coupled receptors, DP1 and DP2/CRTH2 (chemoattractant receptor homologous molecule expressed on T helper type 2 cells)/GPR44 to show a variety of biological effects. DP1 activation leads to Gs-mediated elevation of the intracellular cAMP level, whereas activation of DP2 decreases this level via the Gi pathway; and it also induces G protein-independent, arrestin-mediated cellular responses...
2017: PloS One
https://www.readbyqxmd.com/read/28392807/efficacy-and-safety-of-setipiprant-in-seasonal-allergic-rhinitis-results-from-phase-2-and-phase-3-randomized-double-blind-placebo-and-active-referenced-studies
#13
Paul Ratner, Charles P Andrews, Frank C Hampel, Bruce Martin, Dale E Mohar, Denis Bourrelly, Parisa Danaietash, Sara Mangialaio, Jasper Dingemanse, Abdel Hmissi, Jay van Bavel
BACKGROUND: Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks. METHODS: A Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season...
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#14
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28299574/physiological-and-pathological-roles-of-15-deoxy-%C3%AE-12-14-prostaglandin-j2-in-the-central-nervous-system-and-neurological-diseases
#15
REVIEW
Tatsurou Yagami, Yasuhiro Yamamoto, Hiromi Koma
Prostaglandins (PGs) are divided into conventional PGs, e.g., PGD2, and cyclopentenone-type PGs, e.g., 15-deoxy-Δ(12,14) prostaglandin J2 (15d-PGJ2). PGD2 is non-enzymatically metabolized to PGJ2, Δ(12)-PGJ2, and 15d-PGJ2. In the central nervous system, 15d-PGJ2 differentiates embryonic midbrain cells into dopaminergic neuronal cells via its nuclear peroxysome proliferator-activated receptor-γ (PPARγ). 15d-PGJ2 exerts conflict actions: proinflammatory and anti-inflammatory activities. In the brain, 15d-PGJ2 possesses opposite functions as a neuroprotectant at low concentrations and a neurotoxicant at high concentrations in the brain...
March 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28222358/tyrosine-kinase-inhibition-is-an-important-factor-for-gene-expression-of-crth2-in-human-eosinophils-and-lymphocytes-a-novel-mechanism-for-explaining-eosinophils-recruitment-by-the-neuro-immune-axis-in-allergic-rhinitis
#16
A E El-Shazly, P Roncarati, M Lejeune, P P Lefebvre, P Delvenne
We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation...
April 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28106273/the-immunoglobulin-superfamily-member-cd200r-identifies-cells-involved-in-type-2-immune-responses
#17
L H Blom, B C Martel, L F Larsen, C V Hansen, M P Christensen, N Juel-Berg, T Litman, L K Poulsen
BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation. METHODS: Naïve human CD4(+) T cells were short-term activated in the presence or absence of IL-4 and analyzed for expression of >300 cell-surface proteins...
July 2017: Allergy
https://www.readbyqxmd.com/read/28099820/new-and-developing-non-adrenoreceptor-small-molecule-drugs-for-the-treatment-of-asthma
#18
REVIEW
Neil C Thomson
Inhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta2-agonist (LABA) are the preferred long-term treatment for adults and adolescents with symptomatic asthma. Additional drugs include leukotriene-receptor antagonists, slow-release theophylline and the long-acting muscarinic antagonist (LAMA) tiotropium (approved in 2015). There is a need for more effective therapies, as many patients continue to have poorly controlled asthma. Areas covered: New and developing long-acting non-adrenoreceptor synthetic drugs for the treatment of symptomatic chronic asthma despite treatment with an ICS alone or combined with a LABA...
February 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27872865/cxcr3-ccr5-and-crth2-chemokine-receptor-expression-in-lymphocytes-infiltrating-thyroid-nodules-with-coincident-hashimoto-s-thyroiditis-obtained-by-fine-needle-aspiration-biopsy
#19
Jan Jiskra, Marie Antošová, Jan Krátký, Hana Vítková, Zdeňka Límanová, Helena Marečková, Eliška Potluková
Objective. To determine the expression of chemokine receptors in lymphocytes from thyroid nodules and peripheral blood in patients with and without Hashimoto's thyroiditis (HT). Patients and Methods. The study included 46 women with thyroid nodules and HT and 60 women with thyroid nodules without HT (controls) who underwent a fine needle aspiration biopsy (FNAB). Expression of chemokine receptors CXCR3, CCR5, and CRTH2 was assessed by flow cytometry in lymphocytes from FNAB samples and from peripheral blood...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27735066/anti-inflammatory-therapies-in-atopic-dermatitis
#20
REVIEW
A Heratizadeh, T Werfel
The pathogenesis of atopic dermatitis (AD) is multifactorial and complex. Consequently, clinical signs and symptoms vary strongly depending on individually relevant trigger factors and the stage of the disease. So far, treatment of AD was commonly limited to topical treatment or, in more severe cases, to systemic drugs mostly approved for other indications than AD. However, emerging data on new anti-inflammatory agents have been published in the recent years. As these new substances specifically focus on immune responses in AD, these are partially considered as possible 'breakthrough' in the treatment of AD...
December 2016: Allergy
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