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CRTH2 receptor

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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
#1
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
#2
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
#3
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
#4
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
#5
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...
February 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28106273/the-immunoglobulin-superfamily-member-cd200r-identifies-cells-involved-in-type-2-immune-responses
#6
Lars H Blom, Britta C Martel, Lau F Larsen, Camilla V Hansen, Malene P Christensen, Nanna Juel-Berg, Thomas Litman, Lars 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 analysed for expression of >300 cell-surface proteins...
January 20, 2017: Allergy
https://www.readbyqxmd.com/read/28099820/new-and-developing-non-adrenoreceptor-small-molecule-drugs-for-the-treatment-of-asthma
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27621597/two-phase-ii-randomized-trials-on-the-crth2-antagonist-azd1981-in-adults-with-asthma
#10
RANDOMIZED CONTROLLED TRIAL
Piotr Kuna, Leif Bjermer, Göran Tornling
BACKGROUND: Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cell (CRTh2) receptor antagonists is being investigated for asthma. OBJECTIVES: The aim of this study was to assess the effects of the CRTh2 receptor antagonist, AZD1981 (with/without inhaled corticosteroids [ICSs]), on lung function and asthma control. PATIENTS AND METHODS: Adults aged 18-60 years were enrolled in two randomized, placebo-controlled, parallel-group trials (protocol number: D9830C00003 [study 1, n=209] and protocol number: D9830C00004 [study 2, n=510])...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27558866/an-s-warfarin-and-azd1981-interaction-in-vitro-and-clinical-pilot-data-suggest-the-n-deacetylated-amino-acid-metabolite-as-the-primary-perpetrator
#11
Ken Grime, Rikard Pehrson, Pär Nordell, Michael Gillen, Wolfgang Kühn, Timothy Mant, Marie Brännström, Petter Svanberg, Barry Jones, Clive Brealey
AIM: AZD1981 is an orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist progressed to phase II trials for the treatment of allergic asthma. Previously performed in vitro human hepatocyte incubations identified N-deacetylated AZD1981 as a primary metabolite. We report on metabolite exposure from a clinical excretion balance, on in vitro studies performed to determine the likelihood of a metabolite-dependent drug-drug interaction (DDI) and on a clinical warfarin DDI study...
February 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27525671/assessing-the-new-and-emerging-treatments-for-atopic-dermatitis
#12
Lawrence F Eichenfield, Sheila F Friedlander, Eric L Simpson, Alan D Irvine
The newer and emerging treatments for atopic dermatitis (AD) focus on blockade of inflammatory cytokines, especially those that derive from T helper cell type 2 (TH2) and are associated with a pathway of immunoglobulin E (IgE) sensitization. Among the proinflammatory cytokines that have been identified as promising therapeutic targets are chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2), IgE, thymic stromal lymphopoietin (TSLP), and several monoclonal antibodies that block key cytokine pathways in the innate immune response...
June 2016: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/27498997/discovery-of-anti-inflammatory-role-of-prostaglandin-d2
#13
Takahisa Murata, Toko Maehara
Nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin are one of the most frequently used classes of drug worldwide and inhibit prostaglandin (PG) production by inhibiting cyclooxygenase activity. Although NSAIDs are broadly used against inflammatory diseases, they have side effects including alimentary canal disorders, kidney damage, infection and cardiovascular disorders. Thus, it is necessary to elucidate the pathophysiological role of each PG in various diseases to develop better therapies with fewer and milder side effects...
December 1, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27481693/prostaglandin-d2-signaling-mediated-by-the-crth2-receptor-is-involved-in-mk-801-induced-cognitive-dysfunction
#14
Yusuke Onaka, Norihito Shintani, Takanobu Nakazawa, Takuya Kanoh, Yukio Ago, Toshio Matsuda, Ryota Hashimoto, Kazutaka Ohi, Hiroyuki Hirai, Kin-Ya Nagata, Masataka Nakamura, Atsushi Kasai, Atsuko Hayata-Takano, Kazuki Nagayasu, Kazuhiro Takuma, Asao Ogawa, Akemichi Baba, Hitoshi Hashimoto
Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), which is a second receptor for prostaglandin (PG) D2, is involved in inflammatory responses in peripheral tissue; however, its role in cognitive function remains unclear. Here, we demonstrate that CRTH2 is involved in cognitive function using a well-established animal model of cognitive dysfunction induced by MK-801, an N-methyl-d-aspartate receptor antagonist. Genetic deletion and pharmacological inhibition of CRTH2 suppressed MK-801-induced cognitive dysfunction...
November 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27354118/the-oral-crth2-antagonist-qaw039-fevipiprant-a-phase-ii-study-in-uncontrolled-allergic-asthma
#15
Veit J Erpenbeck, Todor A Popov, David Miller, Steven F Weinstein, Sheldon Spector, Baldur Magnusson, Wande Osuntokun, Paul Goldsmith, Markus Weiss, Jutta Beier
BACKGROUND: There is an unmet medical need for allergic asthma patients who are uncontrolled on conventional therapies. The aim of this study was to collect efficacy and safety data for QAW039, an oral chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist, for the treatment of asthma. METHODS: This was an exploratory phase II, double-blind, randomized, placebo-controlled multi-center study. Patients with mild-to-moderate uncontrolled allergic asthma (N = 170) were either without or weaned off inhaled corticosteroids (ICS) and long-acting β-agonists (LABA) and randomized (1:1) to QAW039 (500 mg once daily) or to placebo for 28 days...
August 2016: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27317944/pharmacological-characterization-of-crth2-antagonist-las191859-long-receptor-residence-time-translates-into-long-lasting-in-vivo-efficacy
#16
Marta Calbet, Miriam Andrés, Clara Armengol, Mónica Bravo, Peter Eichhorn, Rosa López, Vicente García-González, Richard Roberts, Montserrat Miralpeix
The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTh2) is a G protein-coupled receptor expressed on the leukocytes most closely associated with asthma and allergy like eosinophils, mast cells, Th2-lymphocytes and basophils. At present it is clear that CRTh2 mediates most prostaglandin D2 (PGD2) pro-inflammatory effects and as a result antagonists for this receptor have reached asthma clinical studies showing a trend of lung function improvement. The challenge remains to identify compounds with improved clinical efficacy when administered once a day...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27310331/pharmacokinetics-safety-and-tolerability-of-fevipiprant-qaw039-a-novel-crth2-receptor-antagonist-results-from-2-randomized-phase-1-placebo-controlled-studies-in-healthy-volunteers
#17
Veit J Erpenbeck, Eva Vets, Lien Gheyle, Wande Osuntokun, Michael Larbig, Srikanth Neelakantham, David Sandham, Gerald Dubois, Walid Elbast, Paul Goldsmith, Markus Weiss
We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1-3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2 , ∼20 hours). Steady state was achieved in 4 days with <2-fold accumulation. Elimination was partly by renal excretion (≤30% of the dose) and glucuronidation. Food had minimal impact on the PK of fevipiprant, and it was well tolerated at single and multiple oral doses up to 500 mg/day...
July 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27091669/effect-of-prostaglandin-d2-on-vegf-release-by-nasal-polyp-fibroblasts
#18
Kengo Kanai, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Takenori Haruna, Ryotaro Omichi, Sei-Ichiro Makihara, Yuji Hirata, Kazunori Nishizaki
BACKGROUND: Vascular endothelial growth factor (VEGF) is known to be associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). VEGF is produced by a variety of cells including fibroblasts. It was recently reported that prostaglandin (PG) E2 induces VEGF release by nasal polyp fibroblasts. However, little is known regarding possible regulation of VEGF by other PGs. We have reported that molecules that regulate PGD2 metabolism play roles in the pathogenesis of CRS including in local eosinophilia and type 2 cytokine production...
October 2016: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/27079298/elevated-levels-of-circulating-cd4-crth2-t-cells-characterize-severe-asthma
#19
N S Palikhe, C Laratta, D Nahirney, D Vethanayagam, M Bhutani, H Vliagoftis, L Cameron
BACKGROUND: Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a receptor for PGD2 and expressed by T cells, eosinophils, basophils, and ILC2 cells. CRTh2 expression by CD4(+) T cells identifies the Th2 subset, and these cells have been characterized as allergen-specific central memory Th2 cells. Recently, activation of the PGD2 -CRTh2 pathway in the lungs was associated with severe asthma. OBJECTIVE: To assess circulating levels of Th2 cells and related mediators in severe asthma and those who experience asthma exacerbations...
June 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/26995677/prostaglandin-d2-is-a-novel-repressor-of-ifn%C3%AE-induced-indoleamine-2-3-dioxygenase-via-the-dp1-receptor-and-camp-pathway
#20
Nesrine Kamal Bassal, Bernard P Hughes, Maurizio Costabile
Expression of elevated levels of Indoleamine 2,3-dioxygenase (IDO) is well established as a mechanism of cancer induced immunosuppression. Pharmacological inhibition of IDO activity is thus a promising alternative in the treatment of cancer. Previously we demonstrated that cyclooxygenase derived metabolites of arachidonic acid inhibited the interferon-gamma mediated induction of IDO in both THP-1 cells and human monocytes. Here we identified that of the five primary prostanoids produced by COX-1/COX-2, only PGD2 displayed significant repressor activity...
July 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
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