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Il-1 receptor antagonist

Hoon-Seong Choi, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Sheu-Ran Choi, Suk-Yun Kang, Ji-Young Moon, Ho-Jae Han, Hyun-Woo Kim, Alvin J Beitz, Jang-Hern Lee
Although we have recently demonstrated that carrageenan-induced inflammation upregulates the expression of spinal interleukin (IL)-1β, which inhibits spinal astrocyte activation and results in the delayed development of Mirror-Image Pain (MIP), little is known regarding the mechanisms that underlie how spinal IL-1β inhibits the astrocyte activation. In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points...
October 20, 2016: Experimental Neurology
Hoon-Seong Choi, Dae-Hyun Roh, Seo-Yeon Yoon, Soon-Gu Kwon, Sheu-Ran Choi, Suk-Yun Kang, Ji-Young Moon, Ho-Jae Han, Hyun-Woo Kim, Alvin J Beitz, Jang-Hern Lee
Although we have recently demonstrated that carrageenan-induced inflammation upregulates the expression of spinal interleukin (IL)-1β, which inhibits spinal astrocyte activation and results in the delayed development of Mirror-Image Pain (MIP), little is known regarding the mechanisms that underlie how spinal IL-1β inhibits the astrocyte activation. In this study, we examined the effect of spinal IL-1β on astrocyte gap junctions (GJ) and the development of MIP. Following unilateral carrageenan (CA) injection, mechanical allodynia (MA) was evaluated at various time points...
October 20, 2016: Experimental Neurology
Tianwei E Zhou, José C Rivera, Vikrant K Bhosle, Isabelle Lahaie, Zhuo Shao, Houda Tahiri, Tang Zhu, Anna Polosa, Allison Dorfman, Alexandra Beaudry-Richard, Santiago Costantino, Gregory A Lodygensky, Pierre Lachapelle, Sylvain Chemtob
Retinopathy of prematurity (ROP), the most common cause of blindness in premature infants, has long been associated with inner retinal alterations. However, recent studies reveal outer retinal dysfunctions in patients formerly afflicted with ROP. We have recently demonstrated that choroidal involution occurs early in retinopathy. Herein, we investigated the mechanisms underlying the choroidal involution and its long-term impact on retinal function. An oxygen-induced retinopathy (OIR) model was used. In vitro and ex vivo assays were applied to evaluate cytotoxic effects of IL-1β on choroidal endothelium...
October 18, 2016: American Journal of Pathology
Szczepan Mogilski, Monika Kubacka, Dorota Łażewska, Małgorzata Więcek, Monika Głuch-Lutwin, Małgorzata Tyszka-Czochara, Karolina Bukowska-Strakova, Barbara Filipek, Katarzyna Kieć-Kononowicz
OBJECTIVE AND DESIGN: Histamine H4 receptor (H4R) offers a great potential for new therapeutic strategies for the treatment of inflammation-based diseases. The aim of this study is to present the pharmacological profile of two recently synthesized ligands of H4R with particular reference to their anti-inflammatory and analgesic activity. MATERIALS AND SUBJECTS: We used mice and rats in the in vivo tests. We also used murine RAW 264.7 cells and isolated guinea-pig ileum in in vitro test...
October 20, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Ingunn Holen, Diane V Lefley, Sheila E Francis, Sarah Rennicks, Steven Bradbury, Robert E Coleman, Penelope Ottewell
BACKGROUND: We have recently identified interleukin 1B (IL-1B) as a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis. In mouse models, IL-1B and its receptor (IL-1R1) are upregulated in breast cancer cells that metastasise to bone compared with cells that do not. We have now investigated the functional role of IL-1 by blocking IL-1R signalling with the clinically licensed antagonist, anakinra. METHODOLOGY: 6-week old female BALB/c mice received a subcutaneous or intra-venous injection of MDA-MB-231-IV or MCF7 cells...
September 27, 2016: Oncotarget
Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, the metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist, MGS0039 shows antidepressant effects. However, there are no reports comparing these two compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice, after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor (BDNF), TrkB, phospho-TrkB (p-TrkB), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluA1) and postsynaptic density protein 95 (PSD-95), and dendritic spine density in selected brain regions were measured...
October 7, 2016: International Journal of Neuropsychopharmacology
Seok Roh Yoon, Cho Ara, Zhou Zixiong, Jeong Hyuneui, Park Jeong-Eun, Cha Youn-Soo, Oh Suk-Heung, Lim Chae-Woong, Kim Bumseok
<p>Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects...
October 17, 2016: Journal of Biomedical Research
Gabriela Maria Wiedemann, Max Martin Ludwig Knott, Viola Katharina Vetter, Moritz Rapp, Sascha Haubner, Julia Fesseler, Benjamin Kühnemuth, Patrick Layritz, Raffael Thaler, Stephan Kruger, Steffen Ormanns, Doris Mayr, Stefan Endres, David Anz
In cancer patients, immunosuppression through regulatory T cells (Treg) is a crucial component of tumor immune evasion and contributes to disease progression. Tumor-infiltrating Treg in particular suppress local effector T cell responses and are associated with poor prognosis in tumors such as human pancreatic cancer or hepatocellular carcinoma (HCC). The chemokine CCL22 is known to recruit Treg into the tumor tissue and many types of human tumors are known to express high levels of CCL22. The mechanisms leading to intratumoral secretion of CCL22 are so far unknown...
2016: Oncoimmunology
Claudia Balducci, Angelisa Frasca, Margherita Zotti, Pietro La Vitola, Emanuela Mhillaj, Emanuele Grigoli, Martina Iacobellis, Federica Grandi, Massimo Messa, Laura Colombo, Monica Molteni, Luigia Trabace, Carlo Rossetti, Mario Salmona, Gianluigi Forloni
[Background] Amyloid-β oligomers (AβO) are species mainly involved in the synaptic and cognitive dysfunction in Alzheimer's disease. Although their action has been described mainly at neuronal level, it is now clear that glial cells govern synaptic activity in their resting state, contributing to new learning and memory establishment. In contrast, when activated, they may lead to synaptic and cognitive dysfunction. Using a reliable acute AβO-mediated mouse model of AD, we explored whether the memory alteration AβOs induce relies on the activation of glial cells, and if Toll-like receptor 4 (TLR4), pivotal in the initiation of an immune response, is involved...
October 14, 2016: Brain, Behavior, and Immunity
David Grimaldi, Eduardo Wilfrido Goicoechea Turcott, Fabio Silvio Taccone
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Disease
Aditya Stanam, Katherine N Gibson-Corley, Laurie Love-Homan, Nnamdi Ihejirika, Andrean L Simons
Erlotinib has demonstrated poor clinical response rates for head and neck squamous cell carcinoma (HNSCC) to date and the majority of respondents acquire resistance to erlotinib relatively quickly. To elucidate novel pathways involved in erlotinib resistance, we compared the gene expression profiles of erlotinib-resistant (ER) vs. erlotinib-sensitive (ES) HNSCC cell lines. Enrichment analysis of microarray data revealed a deregulation of the IL-1 signaling pathway in ER versus ES-HNSCC cells. Gene expression of interleukin-1 alpha (IL1A) and interleukin-1 beta (IL1B) were significantly upregulated by > 2 fold in ER-SQ20B and ER-CAL 27 cells compared to their respective ES-cells...
October 12, 2016: Oncotarget
Amir S Yazdi, Kamran Ghoreschi
The interleukin-1 (IL-1) family consists of several pro- or anti-inflammatory proteins, with pro-inflammatory IL-1β being its best characterized member. IL-1β is one of the most prominent mediators of inflammation resulting in fever and immune activation via binding to IL-1 receptor 1. Due to its potency, its secretion is tightly regulated. First the transcription of the biologically inactive proform is induced by TLR activation, TNF, or IL-1 receptor activation by mature IL-1α or IL-1β. For the secretion of IL-1β, inflammasome activation as second stimulus is needed...
2016: Advances in Experimental Medicine and Biology
Quratulane Gillani, Muhammad Ali, Furhan Iqbal
Interleukin (IL) 6 and 18 plays an important role in inflammatory response following hypoxia ischemia encephalopathy (HIE). Present study was designed to demonstrate the effect of two GABAB receptor antagonists (CGP 35348 and 55845), respectively, on the serum IL6 and IL 18 concentrations in albino mice. Albino mice pups (of both genders) were subjected to Murine model of hypoxia-ischemia encephalopathy on postnatal day 10 (right common carotid artery was ligated followed by 8% hypoxia for 25 minutes). After neonatal brain damage and following weaning, mice were divided in three groups, in gender specific manner, and fed on normal rodent diet till they were 13 week old...
September 2016: Pakistan Journal of Pharmaceutical Sciences
Eun Bong Lee, Nikki Daskalakis, Christine Xu, Anne Paccaly, Barry Miller, Roy Fleischmann, Inga Bodrug, Alan Kivitz
INTRODUCTION: Elevated interleukin (IL)-6 occurs in patients with active rheumatoid arthritis (RA), which has been shown to lead to a decrease in cytochrome P450 (CYP) enzyme activity and alterations in drug concentrations metabolized by CYP. IL-6 signaling blockade by IL-6 receptor (IL-6R) antagonists may reverse this effect of IL-6 and restore CYP activity. This study evaluated the pharmacokinetic profile of simvastatin (a CYP3A4 substrate) before and 1 week after a single dose of sarilumab (a human monoclonal antibody [mAb] blocking the IL-6Rα) in patients with RA, to assess potential interaction...
October 8, 2016: Clinical Pharmacokinetics
Arijit Ghosh, Fang Chen, Feng Wu, Su-Su Tang, Mei Hu, Yan Long, Hong-Bin Sun, Ling-Yi Kong, Hao Hong
Our previous studies showed that cysteinyl leukotrienes receptor 1 (CysLT1R) is upregulated in amyloid-β (Aβ)-induced neurotoxicity and that administration of CysLT1R antagonists such as pranlukast or montelukast can ameliorate memory impairment in mice. In the current study, we sought to explore the role of CysLT1R in intracerebroventricular streptozotocin (STZ-ICV)-induced mouse model of memory impairment and neuroinflammation through shRNA-mediated knockdown of CysLT1R and also its pharmacological blockade by pranlukast...
October 6, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
V Ziaee, M Maddah, S Harsini, A Rezaei, M Sadr, S Zoghi, M H Moradinejad, N Rezaei
BACKGROUND: Cytokines, including interleukin-1 (IL-1), seem to contribute towards the pathogenesis of juvenile idiopathic arthritis (JIA), so this study was designed to evaluate the associations of IL-1 gene cluster and IL-1 receptor (IL-1R) gene single nucleotide polymorphisms (SNPs) with JIA proneness in Iranian population. MATERIALS AND METHODS: Genomic DNA of 55 Iranian patients with JIA and 140 controls were extracted and typed for IL-1α gene at position -889, IL-1β gene at positions -511 and +3962, IL-1R gene at position Pst-I 1970, and interleikin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls...
October 4, 2016: Allergologia et Immunopathologia
Olivier Malaise, Biserka Relic, Edith Charlier, Mustapha Zeddou, Sophie Neuville, Céline Deroyer, Philippe Gillet, Edouard Louis, Michel G Malaise, Dominique de Seny
BACKGROUND: Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of exogenous glucocorticoids in mice arthritis models and GILZ could also mediate some glucocorticoid-related adverse events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to adipokines such as leptin, and we previously observed that glucocorticoids induced leptin secretion in OA synovial fibroblasts...
October 4, 2016: Arthritis Research & Therapy
Aurélie Gabrion, Isabelle Hmitou, Despina Moshous, Bénédicte Neven, Alain Lefèvre-Utile, Jean-Sébastien Diana, Félipe Suarez, Capucine Picard, Stéphane Blanche, Alain Fischer, Marina Cavazzana, Fabien Touzot
BACKGROUND: Chronic granulomatous disease (CGD) is primary immunodeficiency caused by defective production of reactive oxygen species in phagocytic cells that results in life-threatening infections and severe inflammatory manifestations. The treatment of inflammatory manifestations remains challenging, as it can be associated with an increased risk of infections. Previous studies have shown that CGD phagocytes display a defect in autophagy and a reactive oxygen species-independent activation of the inflammasome...
October 1, 2016: Journal of Allergy and Clinical Immunology
Chun Teng Zhang, Jing Ran Lin, Feng Wu, Arijit Ghosh, Su Su Tang, Mei Hu, Yan Long, Hong Bin Sun, Hao Hong
Extensive studies have demonstrated that neuroinflammation is associated with Alzheimer's disease (AD) and cysteinyl leukotriene receptor 1 (CysLT1R) was involved in neuroinflammation. Montelukast, a highly selective CysLT1R antagonist, has been reported to attenuate learning and memory impairments in the amyloid-β-induced mouse model of AD. However, whether montelukast also exerts beneficial effects on streptozotocin (STZ)-induced memory deficits in mice is not well known. In the present study, we aimed to investigate the effects of montelukast on STZ-induced cognitive impairment, neuroinflammation and apoptosis in mice...
October 1, 2016: Neurotoxicology
Stephanie R Harrison, Dennis McGonagle, Sharmin Nizam, Stephen Jarrett, Jeroen van der Hilst, Michael F McDermott, Sinisa Savic
BACKGROUND: Some adult patients presenting with unexplained pyrexia, serositis, skin rashes, arthralgia, myalgia, and other symptoms commonly found in autoinflammatory disorders may not fit a specific diagnosis, either because their clinical phenotype is nondiagnostic or genetic tests are negative. We used the term undifferentiated systemic autoinflammatory disorder (uSAID) to describe such cases. Given that well-defined autoinflammatory diseases show responses to IL-1 blockade, we evaluated whether anakinra was useful for both diagnosing and treating uSAID patients...
May 5, 2016: JCI Insight
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