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IL 17 cytokines receptor and inhibitor

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https://www.readbyqxmd.com/read/29682158/inhibition-of-trpa1-attenuates-doxorubicin-induced-acute-cardiotoxicity-by-suppressing-oxidative-stress-the-inflammatory-response-and-endoplasmic-reticulum-stress
#1
Zhen Wang, Menglong Wang, Jianfang Liu, Jing Ye, Huimin Jiang, Yao Xu, Di Ye, Jun Wan
The transient receptor potential ankyrin 1 (TRPA1) channel is expressed in cardiomyocytes and involved in many cardiovascular diseases. However, the expression and function of TRPA1 in doxorubicin- (Dox-) induced acute cardiotoxicity have not been elucidated. This study aimed at investigating whether blocking the TRPA1 channel with the specific inhibitor HC-030031 (HC) attenuates Dox-induced cardiac injury. The animals were randomly divided into four groups: control, HC, Dox, and Dox + HC. Echocardiography was used to evaluate cardiac function, and the heart was removed for molecular experiments...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29674348/rkip-mediates-autoimmune-inflammation-by-positively-regulating-il-17r-signaling
#2
Wenlong Lin, Ning Wang, Kangxing Zhou, Fasheng Su, Yu Jiang, Jianan Shou, Huan Liu, Chunmei Ma, Youchun Qian, Kai Wang, Xiaojian Wang
Th17 cells contribute to the development of autoimmune diseases by secreting interleukin-17 (IL-17), which activates its receptor (IL-17R) that is expressed on epithelial cells, macrophages, microglia, and resident neuroectodermal cells. However, the mechanisms through which IL-17R-mediated signaling contributes to the development of autoimmune disease have not been completely elucidated. Here, we demonstrate that Raf-1 kinase inhibitor protein (RKIP) deficiency in mice ameliorates the symptoms of experimental autoimmune encephalomyelitis (EAE)...
April 19, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29662452/a-novel-epha2-inhibitor-exerts-beneficial-effects-in-pi-ibs-in-vivo-and-in-vitro-models-via-nrf2-and-nf-%C3%AE%C2%BAb-signaling-pathways
#3
Li Zeng, Kaixue Li, Hong Wei, Jingjing Hu, Lu Jiao, Shaoyong Yu, Ying Xiong
Though the detailed pathological mechanism of post-infectious irritable bowel syndrome (PI-IBS) remains unclear, accumulating evidence indicates that oxidative stress and inflammation are implicated in the process of PI-IBS. Oxidative stress and inflammation are regulated by Nrf2 and NF-κB signaling pathways, respectively. EphA2, a member of Eph receptor family, promotes oxidative stress and inflammatory responses via regulation of Nrf2 and NF-κB signaling pathways in various types of human diseases. Understanding the mechanisms by which EphA2 regulate oxidative stress and inflammation in PI-IBS is important for the development of new strategies to treat PI-IBS...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29619032/an-autocrine-tnf%C3%AE-tumor-necrosis-factor-receptor-2-loop-promotes-epigenetic-effects-inducing-human-treg-stability-in-vitro
#4
Paulo C M Urbano, Hans J P M Koenen, Irma Joosten, Xuehui He
A crucial issue for Treg-based immunotherapy is to maintain a bona fide Treg phenotype as well as suppressive function during and after ex vivo expansion. Several strategies have been applied to harness Treg lineage stability. For instance, CD28 superagonist stimulation in vitro , in the absence of CD3 ligation, is more efficient in promoting Treg proliferation, and prevention of pro-inflammatory cytokine expression, such as IL-17, as compared to CD3/CD28-stimulated Treg. Addition of the mTOR inhibitor rapamycin to Treg cultures enhances FOXP3 expression and Treg stability, but does impair proliferative capacity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29617412/tissue-inhibitor-of-metalloproteinase-3-timp-3-induces-fas-dependent-apoptosis-in-human-vascular-smooth-muscle-cells
#5
William R English, Heather Ireland-Zecchini, Andrew H Baker, Trevor D Littlewood, Martin R Bennett, Gillian Murphy
Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD)...
2018: PloS One
https://www.readbyqxmd.com/read/29556726/new-treatment-options-for-inflammatory-bowel-diseases
#6
REVIEW
Bram Verstockt, Marc Ferrante, Séverine Vermeire, Gert Van Assche
The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al...
March 19, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29490676/pharmacological-characterisation-of-cr6086-a-potent-prostaglandin-e-2-receptor-4-antagonist-as-a-new-potential-disease-modifying-anti-rheumatic-drug
#7
Gianfranco Caselli, Albino Bonazzi, Marco Lanza, Flora Ferrari, Daniele Maggioni, Cristian Ferioli, Roberto Giambelli, Eleonora Comi, Silvia Zerbi, Marco Perrella, Ornella Letari, Elena Di Luccio, Milena Colovic, Stefano Persiani, Tiziano Zanelli, Laura Mennuni, Tiziana Piepoli, Lucio Claudio Rovati
BACKGROUND: Prostaglandin E2 (PGE2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively...
March 1, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29485127/norepinephrine-inhibits-th17-cells-via-%C3%AE-2-adrenergic-receptor-%C3%AE-2-ar-signaling-in-a-mouse-model-of-rheumatoid-arthritis
#8
Yan Liu, Xiao-Xiao Rui, Hui Shi, Yi-Hua Qiu, Yu-Ping Peng
BACKGROUND Norepinephrine (NE), a neurotransmitter released from the sympathetic nerves, has been shown to be involved in rheumatoid arthritis (RA). However, its role in the sympathetic nervous system in RA is divergent. Herein, we demonstrate that the sympathetic neurotransmitter NE exerts an anti-inflammatory effect in collagen-induced arthritis (CIA), a mouse model of RA, by inhibiting Th17 cell differentiation and function via β2-adrenergic receptor (β2-AR) signaling. MATERIAL AND METHODS CIA was prepared by intradermal injection of collagen type II in the tail base of DBA1/J mice...
February 27, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29371916/the-il-17b-il-17-receptor-b-pathway-promotes-resistance-to-paclitaxel-in-breast-tumors-through-activation-of-the-erk1-2-pathway
#9
Emilie Laprevotte, Stéphanie Cochaud, Stanislas du Manoir, Marion Lapierre, Cécile Dejou, Marion Philippe, Jérome Giustiniani, Kathryn A Frewer, Andrew J Sanders, Wen G Jiang, Henri-Alexandre Michaud, Pierre-Emmanuel Colombo, Armand Bensussan, Gilles Alberici, Jérémy Bastid, Jean-François Eliaou, Nathalie Bonnefoy
Interleukin 17B (IL-17B) is a pro-inflammatory cytokine that belongs to the IL-17 cytokines family and binds to IL-17 receptor B (IL-17RB). Here we found that high expression of IL-17B and IL-17RB is associated with poor prognosis in patients with breast cancer and that IL-17B expression upregulation is specifically associated with poorer survival in patients with basal-like breast cancer. We thus focused on IL-17B role in breast cancer by using luminal and triple negative (TN)/basal-like tumor cell lines. We found that IL-17B induces resistance to conventional chemotherapeutic agents...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29233615/diet-quality-inflammation-and-quality-of-life-in-breast-cancer-survivors-a-cross-sectional-analysis-of-pilot-study-data
#10
Tonya S Orchard, Rebecca R Andridge, Lisa D Yee, Maryam B Lustberg
BACKGROUND: Modifiable lifestyle factors, such as diet quality, could reduce inflammation and improve quality of life (QOL) in breast cancer survivors, but data are inconclusive. OBJECTIVE: To determine whether diet quality, as measured by Healthy Eating Index-2010 (HEI-2010) score, is associated with inflammation, health status, or functional outcomes affecting QOL in survivors of early-stage breast cancer. DESIGN: This is a cross-sectional, secondary analysis of baseline data collected from breast cancer survivors after completion of primary therapy and before random assignment to a pilot nutritional intervention aimed at reducing side effects of aromatase inhibitor treatment...
December 9, 2017: Journal of the Academy of Nutrition and Dietetics
https://www.readbyqxmd.com/read/29128193/vitamin-d-levels-vitamin-d-receptor-polymorphisms-and-inflammatory-cytokines-in-aromatase-inhibitor-induced-arthralgias-an-analysis-of-cctg-ma-27
#11
Polly Niravath, Bingshu Chen, Judy-Anne W Chapman, Sandeep K Agarwal, Robert L Welschhans, Tim Bongartz, Krishna R Kalari, Lois E Shepherd, John Bartlett, Kathleen Pritchard, Karen Gelmon, Susan G Hilsenbeck, Mothaffar F Rimawi, C Kent Osborne, Paul E Goss, James N Ingle
BACKGROUND: Approximately half of women taking aromatase inhibitor (AI) therapy develop AI-induced arthralgia (AIA), and many might discontinue AI therapy because of the pain. Using plasma samples from the MA.27 study, we assessed several factors potentially associated with AIA. PATIENTS AND METHODS: MA.27 is a phase III adjuvant trial comparing 2 AIs, exemestane versus anastrozole. Within an 893-participant nested case-control AIA genome-wide association study, we nested a 72 AIA case-144 control assessment of vitamin D plasma concentrations, corrected for seasonal and geographic variation...
February 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29058501/review-of-il-17-inhibitors-for-psoriasis
#12
Mina Amin, Kavita Darji, Daniel J No, Tina Bhutani, Jashin J Wu
BACKGROUND: The development of biologic agents directed against distinct cytokines and receptors has advanced the therapeutic options available for psoriasis patients. Evidence from preclinical studies suggests that IL-17 may contribute to the pathogenesis of psoriasis. OBJECTIVE: The objective was to review the safety and efficacy profile for each IL-17 inhibitor by evaluating phase III clinical trial data. METHODS: We reviewed the results of phase III clinical trials for the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab...
November 10, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29021166/an-analysis-of-il-36-signature-genes-and-individuals-with-il1rl2-knockout-mutations-validates-il-36-as-a-psoriasis-therapeutic-target
#13
Satveer K Mahil, Marika Catapano, Paola Di Meglio, Nick Dand, Helena Ahlfors, Ian M Carr, Catherine H Smith, Richard C Trembath, Mark Peakman, John Wright, Francesca D Ciccarelli, Jonathan N Barker, Francesca Capon
Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (TH17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28983980/three-cases-of-facial-erythema-with-dryness-and-pruritus-in-psoriasis-patients-during-treatment-with-il-17-inhibitors
#14
LETTER
T Oiwa, T Honda, A Otsuka, K Kabashima
No abstract text is available yet for this article.
October 6, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28791896/biologics-that-inhibit-the-th17-pathway-and-related-cytokines-to-treat-inflammatory-disorders
#15
REVIEW
Anna Balato, Emanuele Scala, Nicola Balato, Giuseppina Caiazzo, Roberta Di Caprio, Giuseppe Monfrecola, Annunziata Raimondo, Serena Lembo, Fabio Ayala
Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors. Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target...
November 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28736556/ras-signaling-inhibitors-attenuate-disease-in-adjuvant-induced-arthritis-via-targeting-pathogenic-antigen-specific-th17-type-cells
#16
Morad Zayoud, Victoria Marcu-Malina, Einav Vax, Jasmine Jacob-Hirsch, Galit Elad-Sfadia, Iris Barshack, Yoel Kloog, Itamar Goldstein
The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28662824/matrix-metalloproteinases-and-synovial-joint-pathology
#17
Charles J Malemud
Matrix metalloproteinases (MMPs) are zinc-dependent enzymes. These enzymes play a critical role in the destruction of articular cartilage in rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), and the spondyloarthropathies. MMP gene expression is upregulated in these synovial joint pathologies in response to elevated levels of proinflammatory cytokines and soluble mediators such as tumor necrosis factor-α, interleukin-1 (IL-1), IL-6, IL-17, and interferon-γ. These molecules are capable of activating the mitogen-activated protein kinase and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways by binding the cytokine to their respective receptors on immune cells, macrophages, chondrocytes, synoviocytes, and osteocytes leading to increased synthesis of MMPs...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28648837/integrative-characterization-of-chronic-cigarette-smoke-induced-cardiopulmonary-comorbidities-in-a-mouse-model
#18
Ágnes Kemény, Kata Csekő, István Szitter, Zoltán V Varga, Péter Bencsik, Krisztina Kiss, Róbert Halmosi, László Deres, Krisztián Erős, Anikó Perkecz, László Kereskai, Terézia László, Tamás Kiss, Péter Ferdinandy, Zsuzsanna Helyes
Cigarette smoke-triggered inflammatory cascades and consequent tissue damage are the main causes of chronic obstructive pulmonary disease (COPD). There is no effective therapy and the key mediators of COPD are not identified due to the lack of translational animal models with complex characterization. This integrative chronic study investigated cardiopulmonary pathophysiological alterations and mechanisms with functional, morphological and biochemical techniques in a 6-month-long cigarette smoke exposure mouse model...
October 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28625129/triamcinolone-acetonide-suppresses-inflammation-and-facilitates-vascular-barrier-function-in-human-retinal-microvascular-endothelial-cells
#19
Shunsuke Imai, Tomohiro Otsuka, Akira Naito, Masamitsu Shimazawa, Hideaki Hara
BACKGROUND: Diabetic macular edema (DME) is resulted from the retinal microvascular leakage that accompanies the breakdown of blood-retinal barrier. Triamcinolone acetonide (TA) is a therapeutic agent for DME, but since the detailed mechanism of action of TA is not known, part of its action was examined. METHODS: In vitro model to enhance the permeability of human retinal microvascular endothelial cells (HRMECs) was constructed by using DME-related cytokines such as vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)...
2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28535470/pharmacophore-guided-discovery-of-small-molecule-interleukin-15-inhibitors
#20
Barbara Żyżyńska-Granica, Bartosz Trzaskowski, Szymon Niewieczerzał, Sławomir Filipek, Oliwia Zegrocka-Stendel, Małgorzata Dutkiewicz, Piotr Krzeczyński, Magdalena Kowalewska, Katarzyna Koziak
Upregulation of interleukin 15 (IL-15) contributes directly i.a. to the development of inflammatory and autoimmune diseases. Selective blockade of IL-15 aimed to treat rheumatoid arthritis, psoriasis and other IL-15-related disorders has been recognized as an efficient therapeutic method. The aim of the study was to identify small molecules which would interact with IL-15 or its receptor IL-15Rα and inhibit the cytokine's activity. Based on the crystal structure of IL-15Rα·IL-15, we created pharmacophore models to screen the ZINC database of chemical compounds for potential IL-15 and IL-15Rα inhibitors...
August 18, 2017: European Journal of Medicinal Chemistry
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