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Il-1 receptor antagonist

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https://www.readbyqxmd.com/read/28107570/efficacy-and-safety-of-interleukin-17-antagonists-in-patients-with-plaque-psoriasis-a-meta-analysis-from-phase-3-randomized-controlled-trails
#1
Dan Wu, Si-Yuan Hou, Shuai Zhao, Lin-Xin Hou, Ting Jiao, Nan-Nan Xu, Ning Zhang
BACKGROUND: The interleukin-17 (IL-17) cytokine pathway plays a key role in the development of psoriasis. Antibodies targeting IL-17 or blocking its receptor may be a new therapeutic approach for psoriasis. To assist treatment selection in daily practice it is essential to understand the benefit and risk profile of IL-17 antagonists. OBJECTIVE: We performed a meta-analysis to evaluate the efficacy and safety of IL-17 antagonists in patients with psoriasis. METHODS: We searched a number of databases for relevant randomized clinical trials (RCTs) published before May 2016...
January 20, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28106157/tlr4-antagonist-fp7-inhibits-lps-induced-cytokine-production-and-glycolytic-reprogramming-in-dendritic-cells-and-protects-mice-from-lethal-influenza-infection
#2
Laure Perrin-Cocon, Anne Aublin-Gex, Stefania E Sestito, Kari Ann Shirey, Mira C Patel, Patrice André, Jorge C Blanco, Stefanie N Vogel, Francesco Peri, Vincent Lotteau
Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC50 < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS)...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088327/cftr-impairment-upregulates-c-src-activity-through-il-1%C3%AE-autocrine-signaling
#3
María Macarena Massip-Copiz, Mariángeles Clauzure, Ángel Gabriel Valdivieso, Tomás Antonio Santa-Coloma
Cystic Fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Previously, we found several genes showing a differential expression in CFDE cells (epithelial cells derived from a CF patient). One corresponded to c-Src; its expression and activity was found increased in CFDE cells, acting as a signaling molecule between the CFTR activity and MUC1 overexpression. Here we report that bronchial IB3-1 cells (CF cells) also showed increased c-Src activity compared to 'CFTR-corrected' S9 cells...
January 11, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28078079/looking-forward-to-new-targeted-treatments-for-chronic-spontaneous-urticaria
#4
REVIEW
Emek Kocatürk, Marcus Maurer, Martin Metz, Clive Grattan
The introduction of omalizumab to the management of chronic spontaneous urticaria (CSU) has markedly improved the therapeutic possibilities for both, patients and physicians dealing with this disabling disease. But there is still a hard core of patients who do not tolerate or benefit from existing therapies and who require effective treatment. Novel approaches include the use of currently available drugs off-licence, investigational drugs currently undergoing clinical trials and exploring the potential for therapies directed at pathophysiological targets in CSU...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/28066142/participation-of-central-gabaa-receptors-in-the-trigeminal-processing-of-mechanical-allodynia-in-rats
#5
Min Ji Kim, Young Hong Park, Kui Ye Yang, Jin Sook Ju, Yong Chul Bae, Seong Kyu Han, Dong Kuk Ahn
Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28063227/lipus-suppressed-lps-induced-il-1%C3%AE-through-the-inhibition-of-nf-%C3%AE%C2%BAb-nuclear-translocation-via-at1-plc%C3%AE-pathway-in-mc3t3-e1
#6
Mayu Nagao, Natsuko Tanabe, Soichiro Manaka, Masako Naito, Kumiko Nakai, Tadahiro Takayama, Takayuki Kawato, Go Torigoe, Jumpei Sekino, Naoya Tsukune, Masao Maeno, Naoto Suzuki, Shuichi Sato
Inflammatory cytokines, interleukin (IL)-1, IL-6, and TNF-a, are involved in inflammatory bone diseases such as rheumatoid osteoarthritis and periodontal disease. Particularly, periodontal disease, which destroys alveolar bone, is stimulated by lipopolysaccharide (LPS). Low-intensity pulsed ultrasound (LIPUS) is used for bone healing in orthopedics and dental treatments. However,the mechanism underlying effects of LIPUS on LPS-induced inflammatory cytokine are not well understood. We therefore aimed to investigate the role of LIPUS on LPS-induced IL-1a production...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28058779/dual-role-of-il-1%C3%AE-in-islet-amyloid-formation-and-its-%C3%AE-cell-toxicity-implications-in-type-2-diabetes-and-islet-transplantation
#7
Yoo Jin Park, Garth L Warnock, Ziliang Ao, Nooshin Safikhan, Mark Meloche, Ali Asadi, Timothy J Kieffer, Lucy Marzban
AIMS/HYPOTHESIS: Islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to β-cell failure in type 2 diabetes, cultured and transplanted islets. We previously showed that biosynthetic hIAPP aggregates induce β-cell Fas upregulation and activation of the Fas apoptotic pathway. Here, we used cultured human and hIAPP-expressing mouse islets to investigate: (1) the role of IL-1β in amyloid-induced Fas upregulation; (2) the effects of IL-1β-induced β-cell dysfunction on proIAPP processing and amyloid formation...
January 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28056339/asbestos-induced-mesothelial-to-fibroblastic-transition-is-modulated-by-the-inflammasome
#8
Joyce K Thompson, Maximilian B MacPherson, Stacie L Beuschel, Arti Shukla
Despite the causal relationship established between malignant mesothelioma (MM) and asbestos exposure, the exact mechanism by which asbestos induces this neoplasm and other asbestos-related diseases is still not well understood. MM is characterized by chronic inflammation, which is believed to play an intrinsic role in the origin of this disease. We recently found that asbestos activates the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in a protracted manner, leading to an up-regulation of IL-1β and IL-18 production in human mesothelial cells...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28054242/anti-nociceptive-and-anti-inflammatory-actions-of-sulforaphane-in-chronic-constriction-injury-induced-neuropathic-pain-mice
#9
Cheng Wang, Congpin Wang
Neuropathic pain is still considered as incurable disease as current therapies are not ideal in terms of efficacy and tolerability. It is imperative to search for novel drugs to obtain better treatments. Sulforaphane (SFN), a derivative of glucoraphanin present in cruciferous vegetables, exhibits therapeutic effects on inflammation-related diseases. Since inflammation plays an important role in regulating chronic pain, in the present study, we investigated anti-nociceptive effects of SFN and its underlying mechanisms in a neuropathic pain mouse model, sciatic nerve chronic constriction injury (CCI)...
January 4, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28052869/nlrp3-inflammasome-activation-contributes-to-aldosterone-induced-podocyte-injury
#10
Mi Bai, Ying Chen, Min Zhao, Yue Zhang, John Cijiang He, Songming Huang, Zhanjun Jia, Aihua Zhang
Aldosterone (Aldo) has been shown as an important contributor of podocyte injury. However, the underlying molecular mechanisms are still elusive. Recently, the pathogenic role of NLRP3 inflammasome in mediating renal tubular damage was identified while its role in podocyte injury still needs evidence. Thus the present study was undertaken to investigate the role of NLRP3 inflammasome in Aldo-induced podocyte damage. In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1 and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by a mineralocorticoid receptor antagonist Eplerenone (EPL) or an antioxidant NAC...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28032234/the-emerging-role-of-interleukin-il-1-in-the-pathogenesis-and-treatment-of-inflammatory-and-degenerative-eye-diseases
#11
Claudia Fabiani, Jurgen Sota, Gian Marco Tosi, Rossella Franceschini, Bruno Frediani, Mauro Galeazzi, Donato Rigante, Luca Cantarini
Interleukin (IL)-1 plays a key role in the pathogenesis and thereafter in the search for specific treatments of different inflammatory and degenerative eye diseases. Indeed, an overactivity of IL-1 might be an initiating factor for many immunopathologic sceneries in the eye, as proven by the efficacy of the specific IL-1 blockade in different ocular diseases. For instance, the uveitis in monogenic autoinflammatory disorders, such as Blau syndrome and cryopyrin-associated periodic syndrome, or in complex polygenic autoinflammatory disorders, such as Behçet's disease, has been successfully treated with IL-1 blockers...
December 28, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/28028363/c5a-c5ar-pathway-is-essential-for-up-regulating-sphk1-expression-through-p38-mapk-activation-in-acute-liver-failure
#12
Yan-Chang Lei, Chun-Lei Lu, Ling Chen, Ke Ge, Ling-Ling Yang, Wen Li, Yuan-Hua Wu
AIM: To investigate the role of the complement 5a (C5a)/C5a receptor (C5aR) pathway in the pathogenesis of acute liver failure (ALF) in a mouse model. METHODS: BALB/c mice were randomly assigned to different groups, and intraperitoneal injections of lipopolysaccharide (LPS)/D-galactosamine (D-GalN) (600 mg/kg and 10 μg/kg) were used to induce ALF. The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) levels, at different time points within a 1-wk period, were detected with a biochemistry analyzer...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28027695/inhibitory-mechanism-of-the-outer-membrane-growth-of-chronic-subdural-hematomas
#13
Koji Osuka, Yasuo Watanabe, Nobuteru Usuda, Masahiro Aoyama, Kenichiro Iwami, Mikinobu Takeuchi, Takeya Watabe, Masakazu Takayasu
We previously demonstrated that the inflammatory cytokine interleukin-6 (IL-6) activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in fibroblasts within the outer membranes of chronic subdural hematomas (CSDHs), and the activation of this pathway may induce CSDH outer membrane growth. The inhibitory system for this signal transduction pathway is unknown. CSDH fluids were obtained from ten patients during trepanation surgery as the case group, and CSF samples were obtained from seven patients suffering from subarachnoid hemorrhage (SAH) on day 1 as the control group...
December 27, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28018220/the-angiotensin-1-7-mas-axis-counteracts-angiotensin-ii-dependent-and-independent-pro-inflammatory-signaling-in-human-vascular-smooth-muscle-cells
#14
Laura A Villalobos, Álvaro San Hipólito-Luengo, Mariella Ramos-González, Elena Cercas, Susana Vallejo, Alejandra Romero, Tania Romacho, Raffaele Carraro, Carlos F Sánchez-Ferrer, Concepción Peiró
Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28012280/whey-and-casein-proteins-and-medium-chain-saturated-fatty-acids-from-milk-do-not-increase-low-grade-inflammation-in-abdominally-obese-adults
#15
Mette Bohl, Ann Bjørnshave, Søren Gregersen, Kjeld Hermansen
BACKGROUND: Low-grade inflammation is involved in the development of diabetes and cardiovascular disease (CVD). Inflammation can be modulated by dietary factors. Dairy products are rich in saturated fatty acids (SFA), which are known to possess pro-inflammatory properties. However, different fatty acid compositions may exert different effects. Other components such as milk proteins may exert anti-inflammatory properties which may compensate for the potential negative effects of SFAs. Generally, the available data suggest a neutral role of dairy product consumption on inflammation...
July 2016: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28011791/maternal-smoking-and-newborn-cytokine-and-immunoglobulin-levels
#16
Nikhita Chahal, Alexander C McLain, Akhgar Ghassabian, Kara A Michels, Erin M Bell, David A Lawrence, Edwina H Yeung
INTRODUCTION: Prenatal smoking exposure may lead to permanent changes in neonatal inflammation and immune response that have lifelong implications, including increased risks for atopy and respiratory disorders. METHODS: The effect of maternal smoking on neonatal biomarkers of inflammation and immune response was assessed among 3459 singletons and twins in the Upstate KIDS Study. The following inflammatory biomarkers were measured using newborn dried blood spots (DBSs): interleukin (IL)-1α, IL-1 receptor antagonist, IL-6, IL-8, C-reactive protein, and tumor necrosis factor alpha...
December 23, 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28009628/enhanced-delivery-of-il-1-receptor-antagonist-to-the-cns-as-a-novel-anti-tfr-il-1ra-fusion-reverses-neuropathic-mechanical-hypersensitivity
#17
Carl I Webster, Jon Hatcher, Matthew Burrell, George Thom, Peter Thornton, Ian Gurrell, Iain Chessell
Neuropathic pain is a major unmet medical need, with only 30-35 % of patients responding to the current standard of care. The discovery and development of novel therapeutics to address this unmet need have been hampered by poor target engagement, the selectivity of novel molecules, and limited access to the relevant compartments. Biologic therapeutics, either monoclonal antibodies (mAb) or peptides, offer a solution to the challenge of specificity as the intrinsic selectivity of these kinds of molecules is significantly higher than traditional medicinal chemistry-derived approaches...
December 20, 2016: Pain
https://www.readbyqxmd.com/read/28005706/endothelin-type-a-receptor-blockade-reduces-vascular-calcification-and-inflammation-in-rats-with-chronic-kidney-disease
#18
Richard Larivière, Alexandra Gauthier-Bastien, Roth-Visal Ung, Julie St-Hilaire, Fabrice Mac-Way, Darren E Richard, Mohsen Agharazii
OBJECTIVE: Arterial stiffness and calcification are nontraditional cardiovascular risk factors in chronic kidney disease (CKD). Using a rat model of CKD with mineral imbalance, medial vascular calcification has been associated with inflammation and increased endothelin-1 (ET-1) production. We therefore hypothesized that ET-1, through the endothelin type A (ETA) receptor, induces vascular inflammation, calcification and stiffness in CKD. METHODS: CKD was induced in Wistar rats by renal mass ablation...
February 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28004759/blocking-triggering-receptor-expressed-on-myeloid-cells-1-attenuates-lipopolysaccharide-induced-acute-lung-injury-via-inhibiting-nlrp3-inflammasome-activation
#19
Tian Liu, Yong Zhou, Ping Li, Jia-Xi Duan, Yong-Ping Liu, Guo-Ying Sun, Li Wan, Liang Dong, Xiang Fang, Jian-Xin Jiang, Cha-Xiang Guan
Acute lung injury (ALI) is associated with high mortality and uncontrolled inflammation plays a critical role in ALI. TREM-1 is an amplifier of inflammatory response, and is involved in the pathogenesis of many infectious diseases. NLRP3 inflammasome is a member of NLRs family that contributes to ALI. However, the effect of TREM-1 on NLRP3 inflammasome and ALI is still unknown. This study aimed to determine the effect of TREM-1 modulation on LPS-induced ALI and activation of the NLRP3 inflammasome. We showed that LR12, a TREM-1 antagonist peptide, significantly improved survival of mice after lethal doses of LPS...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27996167/intracellular-chloride-concentration-changes-modulate-il-1%C3%AE-expression-and-secretion-in-human-bronchial-epithelial-cultured-cells
#20
Mariángeles Clauzure, Ángel G Valdivieso, María M Massip-Copiz, Consuelo Mori, Andrea V Dugour, Juan M Figueroa, Tomás A Santa Coloma
Cystic fibrosis (CF) is caused by mutations in the CFTR gene, which encodes a cAMP-regulated chloride channel. Several cellular functions are altered in CF cells. However, it is not clear how the CFTR failure induces those alterations. We have found previously several genes differentially expressed in CF cells, including c-Src, MUC1, MTND4 and CISD1 (CFTR-dependent genes). Recently, we also reported the existence of several chloride-dependent genes, among them GLRX5 and RPS27. Here, varying the intracellular chloride concentration [Cl(-) ]i of IB3-1 CF bronchial epithelial cells, we show that IL-1β mRNA expression and secretion are also under Cl(-) modulation...
December 20, 2016: Journal of Cellular Biochemistry
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