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Il-1 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/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
#2
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/28521244/cholecystokinin-protects-mouse-liver-against-ischemia-and-reperfusion-injury
#3
Ying Zhang, Jiali Zhu, Long Guo, Yun Zou, Fang Wang, Han Shao, Jinbao Li, Xiaoming Deng
BACKGROUND: Cholecystokinin (CCK), as a gastrointestinal hormone, has an important protective role against sepsis or LPS-induced endotoxic shock. We aim to address the role of CCK in hepatic ischemia followed by reperfusion (I/R) injury. MATERIALS AND METHODS: A murine model of 60min partial hepatic ischemia followed by 6h of reperfusion was used in this study. CCK and CCKAR Levels in blood and liver were detected at 3h, 6h, 12h and 24h after reperfusion. Then the mice were treated with CCK or proglumide, a nonspecific CCK-receptor (CCK-R) antagonist...
May 15, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28515924/effect-of-serum-interleukin-1-receptor-antagonist-level-on-survival-of-patients-with-non-small-cell-lung-cancer
#4
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/28515278/critical-role-of-p2y12-receptor-in-regulation-of-th17-differentiation-and-experimental-autoimmune-encephalomyelitis-pathogenesis
#5
Chaoyan Qin, Jinfeng Zhou, Yuan Gao, Weiming Lai, Cuixia Yang, Yingying Cai, Shuai Chen, Changsheng Du
Adenosine 5'-diphosphate is a key endogenous cell-signaling molecule that can activate P2 purinergic receptor family members. ADP-P2Y signaling is reported to be associated with inflammation, but its function in T cell differentiation and autoimmune diseases pathogenesis is unclear. In this study, we found that the P2Y12 receptor was upregulated in the peripheral immune tissues of experimental autoimmune encephalomyelitis (EAE) mice. Deficiency of P2Y12 led to a reduced peak severity and cumulative disease score in EAE mice, followed by a dramatic reduction of leukocyte infiltration and less extensive demyelination...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28508104/quercetin-inhibits-gout-arthritis-in-mice-induction-of-an-opioid-dependent-regulation-of-inflammasome
#6
Kenji W Ruiz-Miyazawa, Larissa Staurengo-Ferrari, Sandra S Mizokami, Talita P Domiciano, Fabiana T M C Vicentini, Doumit Camilios-Neto, Wander R Pavanelli, Phileno Pinge-Filho, Flávio A Amaral, Mauro M Teixeira, Rubia Casagrande, Waldiceu A Verri
We investigated the anti-inflammatory and analgesic effects of quercetin in monosodium urate crystals (MSU)-induced gout arthritis, and the sensitivity of quercetin effects to naloxone, an opioid receptor antagonist. Mice were treated with quercetin, and mechanical hyperalgesia was assessed at 1-24 h after MSU injection. In vivo, leukocyte recruitment, cytokine levels, oxidative stress, NFκB activation, and gp91(phox) and inflammasome components (NLRP3, ASC, Pro-caspase-1, and Pro-IL-1β) mRNA expression by qPCR were determined in the knee joints at 24 h after MSU injection...
May 15, 2017: Inflammopharmacology
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
#7
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/28501482/ciproxifan-improves-cholinergic-transmission-attenuates-neuroinflammation-and-oxidative-stress-but-does-not-reduce-amyloid-level-in-transgenic-mice
#8
Vasudevan Mani, Siti Murnirah Jaafar, Nur Syamimi Mohd Azahan, Kalavathy Ramasamy, Siong Meng Lim, Long Chiau Ming, Abu Bakar Abdul Majeed
AIM: The present study is aimed to investigate the ability of ciproxifan, a histamine H3 receptor antagonist to inhibit β-amyloid (Aβ)-induced neurotoxicity in SK-N-SH cells and APP transgenic mouse model. MATERIALS AND METHODS: In vitro studies was designed to evaluate the neuroprotective effects of ciproxifan in Aβ25-35 - induced SK-N-SH cells. For the in vivo study, ciproxifan (1 and 3mg/kg, i.p.) was administrated to transgenic mice for 15days and behaviour was assessed using the radial arm maze (RAM)...
May 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/28495790/systemic-inflammatory-response-syndrome-related-lymphopenia-is-associated-with-adenosine-a1-receptor-dysfunction
#9
Reut Riff, Yair Cohen, Hadar Eini-Rider, Oshri Naamani, Julia Mazar, Yosef S Haviv, Cidio Chaimovitz, Amos Douvdevani
SIRS is associated with lymphopenia, and prolonged lymphopenia of septic patients has been associated with increased mortality risk. We hypothesize that elevated adenosine during SIRS down-regulates Gi-coupled A1R, which signals an effect that sensitizes a cAMP-dependent lymphotoxic response. In this study, we evaluate the role of adenosine in SIRS-mediated lymphopenia and impaired IL-15 production. Cecal ligation and puncture was used to induce sepsis-associated SIRS in mice. BMDCs were cultured and used to measure the effect of adenosine on IL-15...
May 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28495184/interleukin-1%C3%AE-as-emerging-therapeutic-target-in-hematological-malignancies-and-potentially-in-their-complications
#10
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/28495120/combined-treatment-with-h1-and-h4-receptor-antagonists-reduces-inflammation-in-a-mouse-model-of-atopic-dermatitis
#11
Hanna Köchling, Katrin Schaper, Jenny Wilzopolski, Ralf Gutzmer, Thomas Werfel, Wolfgang Bäumer, Manfred Kietzmann, Kristine Rossbach
BACKGROUND: Histamine 4 receptor (H4R) antagonists are considered as new therapeutics for the treatment of atopic dermatitis (AD) and first clinical trials have already shown promising results. Histamine 1 receptor (H1R) antagonists are traditionally used to treat AD although the evidence for the efficacy is weak. The combined blockade of both, H1R and H4R, might provide synergistic anti-inflammatory. OBJECTIVE: The study was performed to test the anti-inflammatory potential of a combined treatment with an H1R and an H4R antagonist in a mouse AD model...
April 21, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28493563/nalmefene-prevents-alcohol-induced-neuroinflammation-and-alcohol-drinking-preference-in-adolescent-female-mice-role-of-tlr4
#12
Jorge Montesinos, Anabel Gil, Consuelo Guerri
BACKGROUND: We previously showed that, by activating innate immune receptors toll-like 4 (TLR4), adolescent intermittent ethanol exposure causes neuroinflammation, myelin damage and behavioral dysfunctions. Recent findings reveal that clinically-used opioid antagonists naltrexone (NT) and naloxone (NX) inhibit opioid-induced TLR4 signaling, and that NT, NX and nalmefene (NF), the 6-methylene derivative of NX, are able to reduce alcohol drinking escalation. METHODS: NF (0...
May 11, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28492873/sphingosine-1-phosphate-mediates-fibrosis-in-orbital-fibroblasts-in-graves-orbitopathy
#13
JaeSang Ko, Min Kyoung Chae, Joon H Lee, Eun Jig Lee, Jin Sook Yoon
Purpose: To investigate the effect of sphingosine-1-phosphate (S1P) on fibrosis in orbital fibroblasts in Graves' orbitopathy (GO). Methods: Orbital fibroblasts were cultured from orbital adipose/connective tissues of patients with GO and healthy control subjects. Effects of treatment with TGF-β and cigarette smoke extract (CSE) on S1P receptor (S1PR) messenger RNA (mRNA) and S1P expression were evaluated by real-time polymerase chain reaction and Western blotting...
May 1, 2017: Investigative Ophthalmology & Visual Science
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
#14
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/28484006/uric-acid-priming-in-human-monocytes-is-driven-by-the-akt-pras40-autophagy-pathway
#15
Tania O Crişan, Maartje C P Cleophas, Boris Novakovic, Kathrin Erler, Frank L van de Veerdonk, Hendrik G Stunnenberg, Mihai G Netea, Charles A Dinarello, Leo A B Joosten
Metabolic triggers are important inducers of the inflammatory processes in gout. Whereas the high serum urate levels observed in patients with gout predispose them to the formation of monosodium urate (MSU) crystals, soluble urate also primes for inflammatory signals in cells responding to gout-related stimuli, but also in other common metabolic diseases. In this study, we investigated the mechanisms through which uric acid selectively lowers human blood monocyte production of the natural inhibitor IL-1 receptor antagonist (IL-1Ra) and shifts production toward the highly inflammatory IL-1β...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
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
#16
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
#17
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
https://www.readbyqxmd.com/read/28461492/sp-and-il-33-together-markedly-enhance-tnf-synthesis-and-secretion-from-human-mast-cells-mediated-by-the-interaction-of-their-receptors
#18
Alexandra Taracanova, Mihail Alevizos, Anna Karagkouni, Zuiy Weng, Errol Norwitz, Pio Conti, Susan E Leeman, Theoharis C Theoharides
The peptide substance P (SP) and the cytokine tumor necrosis factor (TNF) have been implicated in inflammatory processes. Mast cells are recognized as important in inflammatory responses. Here, we report that IL-33 (30 ng/mL), a member of the IL-1 family of cytokines, administered in combination with SP (1 µM), markedly increase (by 1,000-fold) TNF gene expression in cultured human LAD2 and primary mast cells derived from umbilical cord blood. SP (0.01-1 μM) and IL-33 (1-100 ng/mL) in combination also greatly stimulate TNF secretion (by 4,500-fold)...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28439566/inflammatory-markers-and-risk-for-cognitive-decline-in-chronic-kidney-disease-the-cric-study
#19
Manjula Kurella Tamura, Karman Tam, Eric Vittinghoff, Dominic Raj, Stephen M Sozio, Sylvia E Rosas, Gail Makos, Claudia Lora, Jiang He, Alan S Go, Chi-Yuan Hsu, Kristine Yaffe
INTRODUCTION: Chronic kidney disease (CKD) is associated with an increased risk of cognitive decline, but the mechanisms remain poorly defined. We sought to determine the relation between serum inflammatory markers and risk of cognitive decline among adults with CKD. METHODS: We studied 757 adults aged ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort Cognitive study. We measured interleukin (IL)-1β, IL-1 receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), and fibrinogen in baseline plasma samples...
March 2017: KI Reports
https://www.readbyqxmd.com/read/28438965/radiation-induces-proinflammatory-dysbiosis-transmission-of-inflammatory-susceptibility-by-host-cytokine-induction
#20
Shiran Gerassy-Vainberg, Alexandra Blatt, Yael Danin-Poleg, Katya Gershovich, Edmond Sabo, Alex Nevelsky, Shahar Daniel, Aviva Dahan, Oren Ziv, Rishu Dheer, Maria T Abreu, Omry Koren, Yechezkel Kashi, Yehuda Chowers
OBJECTIVE: Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model. DESIGN: We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial-epithelial co-cultures...
April 24, 2017: Gut
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