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Interleukin receptor antagonist

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https://www.readbyqxmd.com/read/28547650/lysosomal-destabilization-activates-the-nlrp3-inflammasome-in-human-umbilical-vein-endothelial-cells-huvecs
#1
K Kinnunen, N Piippo, S Loukovaara, M Hytti, K Kaarniranta, A Kauppinen
Inflammation is a crucial component in the pathogenesis of many vascular diseases, such as atherosclerosis and diabetes. Inflammasomes are intracellular signalling complexes whose activation promotes inflammation. Nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) is a pattern recognition receptor (PRR) forming the best-known inflammasome. Disturbances in NLRP3 have been associated with multiple diseases. The purpose of this study was to explore the lysosomal destabilization-related NLRP3 inflammasome signaling pathway in human endothelial cells...
May 25, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28536823/efficacy-and-safety-of-anakinra-in-tumor-necrosis-factor-receptor-associated-periodic-syndrome-traps-complicated-by-severe-renal-failure-a-report-after-long-term-follow-up-and-review-of-the-literature
#2
REVIEW
Stefano Gentileschi, Donato Rigante, Antonio Vitale, Jurgen Sota, Bruno Frediani, Mauro Galeazzi, Luca Cantarini
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), caused by mutations in the TNFRSF1A gene, is the most frequent autosomal dominant autonflammatory disease displaying a relevant risk of reactive AA amyloidosis, if left untreated. Our report deals with one adult with TRAPS complicated by amyloidosis-related renal failure, treated with the recombinant human interleukin-1 receptor antagonist anakinra at a higher than conventional dosage. This treatment did not present any adverse event and led remarkably to the disappearance of all TRAPS-related manifestations and prompt decrease of laboratory abnormalities, including proteinuria...
May 23, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28536733/minimally-invasive-sampling-of-interleukin-1-%C3%AE-and-interleukin-1-receptor-antagonist-from-the-skin-a-systematic-review-of-in-vivo-studies-in-humans
#3
Denise Falcone, Pieter Spee, Peter C M van de Kerkhof, Piet E J van Erp
Interleukin-1α (IL-1α) and its receptor antagonist IL-1RA play a pivotal role in skin homeostasis and disease. Although the use of biopsies to sample these cytokines from human skin is widely employed in dermatological practice, knowledge about less invasive, in vivo sampling methods is scarce. The aim of this study was to provide an overview of such methods by systematically reviewing studies in Medline, EMBASE, Web of Science and Cochrane Library using combinations of the terms "IL-1α", IL-1RA", "skin", "human", including all possible synonyms...
May 24, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28536528/rescued-chondrogenesis-of-mesenchymal-stem-cells-under-interleukin-1-challenge-by-foamyviral-interleukin-1-receptor-antagonist-gene-transfer
#4
Nicole Armbruster, Jennifer Krieg, Manuel Weißenberger, Carsten Scheller, Andre F Steinert
Background: Mesenchymal stem cells (MSCs) and their chondrogenic differentiation have been extensively investigated in vitro as MSCs provide an attractive source besides chondrocytes for cartilage repair therapies. Here we established prototype foamyviral vectors (FVV) that are derived from apathogenic parent viruses and are characterized by a broad host range and a favorable integration pattern into the cellular genome. As the inflammatory cytokine interleukin 1 beta (IL1β) is frequently present in diseased joints, the protective effects of FVV expressing the human interleukin 1 receptor antagonist protein (IL1RA) were studied in an established in vitro model (aggregate culture system) of chondrogenesis in the presence of IL1β...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28532837/interleukin-1%C3%AE-system-in-the-oviducts-of-pigs-during-the-oestrous-cycle-and-early-pregnancy
#5
M Martyniak, A Franczak, G Kotwica
Interleukin-1β (IL-1β) acts throughout the IL-1β system, which contains IL-1β and the IL-1β receptor (IL-1R), accessory protein (IL-1RacP), and receptor antagonist (IL-1Ra). In pigs, the expression of the members of the IL-1β system was documented in uterine tissues during the oestrous cycle and early pregnancy, as well as in embryos harvested during the peri-implantation period. In the oviducts of non-gravid and gravid pigs, the expression of the IL-1β system is unknown. Thus, in this study, the expression of the IL-1β system was examined in porcine oviducts harvested on days 2-3 to 18-20 of the oestrous cycle and on days 2-3 to 15-16 of pregnancy...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28527783/identification-of-novel-selective-p2y6-receptor-antagonists-by-high-throughput-screening-assay
#6
Masaaki Ito, Shin-Ichiro Egashira, Kazuki Yoshida, Tomoko Mineno, Kazuo Kumagai, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Michio Ui, Isao Matsuoka
AIMS: The P2Y6 nucleotide receptor is widely involved in inflammatory responses, and is a promising molecular target for the treatment of inflammatory diseases. Although several P2Y6 receptor antagonists have been developed and evaluated thus far, none has successfully been developed into a therapeutic drug. In this study, we explored new promising compounds that inhibit the human P2Y6 receptor. MAIN METHODS: High-throughput screening (HTS) was used to study the effects of various compounds on human P2Y6 receptors expressed in 1321N1 human astrocytoma cells by monitoring intracellular Ca(2+) concentration ([Ca(2+)]i) levels using an FDSS7000 real-time fluorescence detector...
May 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28523588/advances-in-the-development-of-janus-kinase-inhibitors-in-inflammatory-bowel-disease-future-prospects
#7
Mathurin Flamant, Josselin Rigaill, Stephane Paul, Xavier Roblin
Inflammatory bowel disease (IBD) is caused by a dysregulation of the immune system, inducing the production of proinflammatory cytokines and adhesion molecules. A better understanding of the mucosal immune response in IBD has led to the development of new drugs directed at inflammatory cytokines and leukocyte-trafficking molecules. Beyond tumor necrosis factor antagonists and anti-integrin molecules, which act by blocking the interaction between gut-specific lymphocytes and their receptor on vascular endothelium, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway represents a new target in IBD...
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28520640/twenty-four-month-follow-up-of-tocilizumab-therapy-for-refractory-uveitis-related-macular-edema
#8
Marina Mesquida, Blanca Molins, Victor Llorenç, María V Hernández, Gerard Espinosa, Maite Sainz de la Maza, Alfredo Adán
BACKGROUND: To report the 24-month efficacy and safety of the interleukin-6 receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular edema (ME). METHODS: Data were obtained by standardized chart review. Patients with quiescent uveitis seen at a single tertiary referral center, for whom ME was the principal cause of reduced visual acuity. OUTCOME MEASURES: Central foveal thickness measured by optical coherence tomography; degree of anterior and posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6, 12, 18, and 24...
May 16, 2017: Retina
https://www.readbyqxmd.com/read/28515924/effect-of-serum-interleukin-1-receptor-antagonist-level-on-survival-of-patients-with-non-small-cell-lung-cancer
#9
Murat Yigit, Serkan Değirmencioğlu, Erhan Ugurlu, Arzu Yaren
Due to poor prognosis in advanced non-small cell lung cancer (NSCLC), new effective markers are required in the monitoring of the disease. The present study aimed to investigate the association between the serum IL-1 receptor antagonist (IL-1Ra) level, overall survival (OS), and treatment response in NSCLC, and to evaluate the usefulness of the serum IL-1Ra level as a prognostic marker for NSCLC. Eighty patients (72 men and 8 women) and 40 healthy volunteers (13 men and 27 women) were included in the present study...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28512667/involvement-of-leukotriene-b4-released-from-keratinocytes-in-itch-associated-response-to-intradermal-interleukin-31-in-mice
#10
Tsugunobu Andoh, Ayako Harada, Yasushi Kuraishi
A recent study suggests that interleukin-31 (IL-31) exerts its effect via indirect mechanisms rather than through direct stimulation of cutaneous nerves. However, the underlying peripheral mechanisms of IL-31-induced itch in the skin remain unclear. Therefore, the present study investigated the peripheral mechanisms underlying IL-31-induced itch in mice. IL-31-induced itch-related response was inhibited by anti-allergic drugs (tranilast and azelastine), but not by an H1 histamine receptor antagonist (terfenadine)...
May 17, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28503715/deficiency-of-interleukin-1-receptor-antagonist-dira-report-of-the-first-indian-patient-and-a-novel-deletion-affecting-il1rn
#11
Leonardo O Mendonca, Louise Malle, Frank X Donovan, Settara C Chandrasekharappa, Gina A Montealegre Sanchez, Megha Garg, Ulf Tedgard, Mariana Castells, Shiv S Saini, Sourabh Dutta, Raphaela Goldbach-Mansky, Deepti Suri, Adriana A Jesus
PURPOSE: Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life-threatening autoinflammatory disease caused by autosomal recessive mutations in IL1RN. DIRA presents clinically with early onset generalized pustulosis, multifocal osteomyelitis, and elevation of acute phase reactants. We evaluated and treated an antibiotic-unresponsive patient with presumed DIRA with recombinant IL-1Ra (anakinra). The patient developed anaphylaxis to anakinra and was subsequently desensitized...
May 15, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28503657/an-amylin-analog-used-as-a-challenge-test-for-alzheimer-s-disease
#12
Haihao Zhu, Robert A Stern, Qiushan Tao, Alexandra Bourlas, Maritza D Essis, Meenakshi Chivukula, James Rosenzweig, Devin Steenkamp, Weiming Xia, Gustavo A Mercier, Yorghos Tripodis, Martin Farlow, Neil Kowall, Wei Qiao Qiu
INTRODUCTION: Preclinical studies demonstrate the potential of amylin in the diagnosis of Alzheimer's disease (AD). We aimed to lay the foundation for repurposing the amylin analog and a diabetes drug, pramlintide, for AD in humans. METHODS: We administered a single subcutaneous injection of 60 μg of pramlintide to nondiabetic subjects under fasting conditions. RESULTS: None of the participants developed hypoglycemia after the injection of pramlintide...
January 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28495184/interleukin-1%C3%AE-as-emerging-therapeutic-target-in-hematological-malignancies-and-potentially-in-their-complications
#13
REVIEW
Lorena Arranz, Maria Del Mar Arriero, Alicia Villatoro
Interleukin-1β (IL-1β) is a pleiotropic cytokine that exerts multiple roles in both physiological and pathological conditions. It is produced by different cell subsets, and drives a wide range of inflammatory responses in numerous target cells. Enhanced IL-1β signaling is a common event in patients of hematological malignancies. Recent body of evidence obtained in preclinical models shows the pathogenic role of these alterations, and the promising therapeutic value of IL-1 targeting. In this review, we further highlight a potential contribution of IL-1β linking to complications and autoimmune disease that should be investigated in future studies...
May 3, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28495142/n-methyl-d-aspartate-receptor-mediated-calcium-overload-and-endoplasmic-reticulum-stress-are-involved-in-interleukin-1beta-induced-neuronal-apoptosis-in-rat-hippocampus
#14
Yilong Dong, Allan V Kalueff, Cai Song
Increased levels of interleukin (IL)-1β and its gene expression are implicated in the etiology of Alzheimer's disease (AD). IL-1β activates microglia and stimulates glutamatergic N-methyl-d-aspartate receptor NMDA receptor expression, thereby disturbing intracellular Ca(2+) homeostasis. Ca(2+) disequilibrium, in turn, may trigger endoplasmic reticulum (ER) stress, contributing to overall excitotoxicity and neuronal death that evoke AD. However, it is unclear whether IL-1β-induced neuronal apoptosis is mediated by the glutamatergic system, ER stress and/or Ca(2+) dysfunction...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28493078/the-5-ht3-receptor-antagonist-ondansetron-attenuates-pancreatic-injury-in-cerulein-induced-acute-pancreatitis-model
#15
Atsushi Tsukamoto, Takuto Sugimoto, Yuta Onuki, Hajime Shinoda, Taiki Mihara, Masatoshi Hori, Tomo Inomata
The 5-hydroxytryptamine-3 receptor (5-HT3R) antagonist ondansetron has been clinically approved as an anti-emetic agent. Recent findings indicate that ondansetron has anti-inflammatory properties. The aim of the present study was to assess the therapeutic action of ondansetron in cerulein-induced acute pancreatitis model. Male-BALB/c mice were used in the present study. Acute pancreatitis was induced by an hourly injection of cerulein. Ondansetron was administered subcutaneously at a dose of 3 mg/kg. The messenger RNA (mRNA) expression of 5-HT3 R in pancreatic tissue was assessed with RT-PCR...
May 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28486969/activation-of-p2x7-receptor-and-nlrp3-inflammasome-assembly-in-hippocampal-glial-cells-mediates-chronic-stress-induced-depressive-like-behaviors
#16
Na Yue, Huijie Huang, Xiaocang Zhu, Qiuqin Han, Yalin Wang, Bing Li, Qiong Liu, Gencheng Wu, Yuqiu Zhang, Jin Yu
BACKGROUND: In recent years, proinflammatory cytokine interleukin-1β (IL-1β) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1β. Here, we investigated the role of P2X7R in the pathogenesis of depression...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28483262/lungs-donated-after-circulatory-death-and-prolonged-warm-ischemia-are-transplanted-successfully-after-enhanced-ex%C3%A2-vivo-lung-perfusion-using-adenosine-a2b-receptor-antagonism
#17
Eric J Charles, J Hunter Mehaffey, Ashish K Sharma, Yunge Zhao, Mark H Stoler, James M Isbell, Christine L Lau, Curtis G Tribble, Victor E Laubach, Irving L Kron
OBJECTIVE: The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. METHODS: Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP...
April 12, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28482330/dienogest-inhibits-c-c-motif-chemokine-ligand-20-expression-in-human-endometriotic-epithelial-cells
#18
Shizuka Mita, Masanori Nakakuki, Masayuki Ichioka, Yutaka Shimizu, Masamichi Hashiba, Hiroyasu Miyazaki, Satoru Kyo
OBJECTIVE: C-C motif chemokine ligand 20 is thought to contribute to the development of endometriosis by recruiting Th17 lymphocytes into endometriotic foci. The present study investigated the effects of dienogest, a progesterone receptor agonist used to treat endometriosis, on C-C motif chemokine ligand 20 expression by endometriotic cells. STUDY DESIGN: Effects of dienogest on mRNA expression and protein secretion of C-C motif chemokine ligand 20 induced by interleukin 1β were assessed in three immortalized endometriotic epithelial cell lines, parental cells (EMosis-CC/TERT1), and stably expressing human progesterone receptor isoform A (EMosis-CC/TERT1/PRA+) or isoform B (EMosis-CC/TERT1/PRA-/PRB+)...
April 29, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28475816/interleukin-1-blockade-in-heart-failure-with-preserved-ejection-fraction-rationale-and-design-of-the-diastolic-heart-failure-anakinra-response-trial-2-d-hart2
#19
Benjamin W Van Tassell, Leo F Buckley, Salvatore Carbone, Cory R Trankle, Justin M Canada, Dave L Dixon, Nayef Abouzaki, Claudia Oddi-Erdle, Giuseppe Biondi-Zoccai, Ross Arena, Antonio Abbate
Heart failure with preserved ejection fraction (HFpEF) now accounts for the majority of confirmed HF cases in the United States. However, there are no highly effective evidence-based treatments currently available for these patients. Inflammation correlates positively with adverse outcomes in HF patients. Interleukin (IL)-1, a prototypical inflammatory cytokine, has been implicated as a driver of diastolic dysfunction in preclinical animal models and a pilot clinical trial. The Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2) is a phase 2, 2:1 randomized, double-blind, placebo-controlled clinical trial that will test the hypothesis that IL-1 blockade with anakinra (recombinant human IL-1 receptor antagonist) improves (1) cardiorespiratory fitness, (2) objective evidence of diastolic dysfunction, and (3) elevated inflammation in patients with HFpEF (http://www...
May 5, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28470940/p2x7-receptor-inhibition-attenuated-sympathetic-nerve-sprouting-after-myocardial-infarction-via-the-nlrp3-il-1%C3%AE-pathway
#20
Jie Yin, Yu Wang, Hesheng Hu, Xiaolu Li, Mei Xue, Wenjuan Cheng, Ye Wang, Xinran Li, Na Yang, Yugen Shi, Suhua Yan
Mounting evidence supports the hypothesis that inflammation modulates sympathetic sprouting after myocardial infarction (MI). The myeloid P2X7 signal has been shown to activate the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a master regulator of inflammation. We investigated whether P2X7 signal participated in the pathogenesis of sympathetic reinnervation after MI, and whether NLRP3/interleukin-1β (IL-1β) axis is involved in the process...
May 4, 2017: Journal of Cellular and Molecular Medicine
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