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Il-1 receptor antagonist

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https://www.readbyqxmd.com/read/29792868/ah6809-decreases-production-of-inflammatory-mediators-by-pge-2-ep2-camp-signaling-pathway-in-an-experimentally-induced-pure-cerebral-concussion-in-rats
#1
Ping Li, Hongyan Jiang, Haiying Wu, Deye Wu, Hengxi Li, Jianyun Yu, Jianghua Lai
Increasing evidence suggests that PGE2 metabolic pathway is involved in pathological changes of the secondary brain injury after traumatic brain injury. However, the underlying mechanisms, in particular, the correlation between various key enzymes and the brain injury, has remained to be fully explored. More specifically, it remains to be ascertained whether AH6809 (an EP2 receptor antagonist) would interfere with the downstream of the PGE2 , regulate the inflammatory mediators and improve neuronal damage in the hippocampus by PGE2 - EP2 - cAMP signaling pathway...
May 21, 2018: Brain Research
https://www.readbyqxmd.com/read/29773988/microglia-p2y-13-receptors-prevent-astrocyte-proliferation-mediated-by-p2y-1-receptors
#2
Clara Quintas, Nuno Vale, Jorge Gonçalves, Glória Queiroz
Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29772075/cd6-mabs-differ-in-epitope-kinetics-and-mechanism-of-action
#3
Lee I Garner, Andrew Hartland, Johannes Breuning, Marion H Brown
CD6 is a type I T cell surface receptor which modulates antigen receptor signalling. Its activity is regulated by binding of its membrane proximal domain (domain 3) to a cell surface ligand, CD166. CD6 monoclonal antibodies (mAbs) specific for the membrane distal domain (domain 1) perturb CD6 function including itolizumab (Alzumab™ ) which has reached the clinic for treatment of autoimmune disease. We characterised molecular and functional properties of several CD6 mAbs including itolizumab to define potential mechanisms of action...
May 17, 2018: Immunology
https://www.readbyqxmd.com/read/29759144/tropisetron-attenuates-lipopolysaccharide-induced-neuroinflammation-by-inhibiting-nf-%C3%AE%C2%BAb-and-sp-nk1r-signaling-pathway
#4
Yan Yu, Wanhu Zhu, Qing Liang, Jing Liu, Xu Yang, Guangchun Sun
Tropisetron, an antagonist of serotonin type 3 receptors (5-HT3 Rs), has been investigated in colonic inflammatory process. Since substance P/neurokinin 1 receptor (SP/NK1R) signaling pathway plays a key role in several sensory neuronal inflammatory. We evaluated the anti-inflammatory activity of tropisetron in mice cerebral cortex, and discovered that it was a potential inhibitor in LPS-mediated neuron inflammation through SP/NK1R signaling pathway. We found that tropisetron significantly reduced the increased number of iba-1 positive microglia, down-regulated the gene transcription and protein expression of IL-1β,IL-6 and TNF-α in LPS stimulated cerebral cortex...
July 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29749433/inhibition-of-interleukin-8-c%C3%A2-x-c-chemokine-receptor-1-2-signaling-reduces-malignant-features-in-human-pancreatic-cancer-cells
#5
Shengling Fu, Xiang Chen, Huey-Jen Lin, Jiayuh Lin
Interactions between interleukin (IL)-8 and its receptors, C‑X-C chemokine receptor 1, (CXCR1) and CXCR2 serve crucial roles in increasing cancer progression. Inhibition of this signaling pathway has yielded promising results in a number of human cancers, including breast, melanoma and colon. However, the effects of CXCR1/2 antagonist treatment on pancreatic cancer remain unclear. The present study aimed to demonstrate that treatment with the clinical grade CXCR1/2 antagonist, reparixin, or the newly discovered CXCR1/2 antagonist, SCH527123, may result in a reduction of the malignant features associated with this lethal cancer...
April 30, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29747742/g-protein-coupled-estrogen-receptor-is-involved-in-the-anti-inflammatory-effects-of-genistein-in-microglia
#6
Zhong-Rui Du, Xiao-Qing Feng, Na Li, Jiang-Xue Qu, Lu Feng, Lei Chen, Wen-Fang Chen
BACKGROUND: Genistein (GEN), a phytoestrogen that is extracted from leguminous plants, can bind to estrogen receptor and exert biological effects. G protein-coupled estrogen receptor (GPER), a novel membrane estrogen receptor, has been reported to be involved in the anti-inflammatory process. In the present study, using BV2 microglial cell line and primary microglial culture, we evaluated the involvement of GPER in the anti-inflammatory effects of genistein against lipopolysaccharide (LPS)-induced microglia activation...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29744290/identification-of-small-molecule-elastase-inhibitors-as-antagonists-of-il-36-cytokine-activation
#7
Graeme P Sullivan, Pavel B Davidovich, Sylvia Sura-Trueba, Ekaterina Belotcerkovskaya, Conor M Henry, Danielle M Clancy, Anna Zinoveva, Tazhir Mametnabiev, Alexander V Garabadzhiu, Seamus J Martin
IL-1 family cytokines act as apical initiators of inflammation in many settings and can promote the production of a battery of inflammatory cytokines, chemokines and other inflammatory mediators in diverse cell types. IL-36α, IL-36β and IL-36γ, which belong to the extended IL-1 family, have been implicated as key initiators of skin inflammation in psoriasis. IL-36γ is highly upregulated in lesional skin from psoriatic individuals, and heritable mutations in the natural IL-36 receptor antagonist result in a severe form of psoriasis...
May 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29742510/hmgb1-a-box-reverses-brain-edema-and-deterioration-of-neurological-function-in-a-traumatic-brain-injury-mouse-model
#8
Lijun Yang, Feng Wang, Liang Yang, Yunchao Yuan, Yan Chen, Gengshen Zhang, Zhenzeng Fan
BACKGROUND/AIMS: Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI...
May 8, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29742501/modulation-of-mast-cell-toll-like-receptor-3-expression-and-cytokines-release-by-histamine
#9
Guogang Xie, Feng Wang, Xia Peng, Yuting Liang, Haiwei Yang, Li Li
BACKGROUND/AIMS: As a major inflammatory molecule released from mast cell activation, histamine has been reported to regulate TLRs expression and cytokine production in inflammatory cells present in the microenvironment. In this study, we determined the ability of histamine to modulate TLRs expression and cytokine production in mast cells. METHODS: HMC-1 and P815 cells were exposed to various concentrations of histamine in the presence or absence of histamine antagonist for 2, 6 or 16 h...
May 4, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29742284/associations-among-human-papillomavirus-inflammation-and-fatigue-in-patients-with-head-and-neck-cancer
#10
Canhua Xiao, Jonathan J Beitler, Kristin A Higgins, Toby Glazer, Linh Kha Huynh, Sudeshna Paul, Jennifer C Felger, Evanthia C Wommack, Nabil F Saba, Dong M Shin, Deborah W Bruner, Andrew H Miller
BACKGROUND: Human papillomavirus (HPV) infection has contributed to an increased incidence of squamous cell carcinoma of the head and neck (SCCHN). Fatigue is a major side effect of SCCHN and its treatment. However, to the authors' knowledge, the association between HPV and fatigue has not been examined to date, nor is it known whether HPV influences biological mechanisms of fatigue, including inflammation. METHODS: Patients with SCCHN who were without distant metastasis were assessed at baseline (pre-radiotherapy) and 1 month and 3 months postradiotherapy...
May 9, 2018: Cancer
https://www.readbyqxmd.com/read/29742056/a-dermatologic-perspective-on-autoinflammatory-diseases
#11
REVIEW
Angelo Valerio Marzano, Giovanni Damiani, Giovanni Genovese, Marco Gattorno
Autoinflammatory diseases (AIDs) encompass a heterogeneous group of disorders pathogenetically related to an abnormal activation of the innate immunity and clinically characterised by aseptic inflammation in the affected organs in the absence of high titer of circulating autoantibodies or autoreactive T cells. In classic monogenic AIDs, the skin is frequently involved with a wide range of cutaneous lesions. Monogenic AIDs result from different mutations in a single gene, which regulates the innate immunity...
January 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29740969/peripheral-cannabinoid-1-receptor-blockade-mitigates-adipose-tissue-inflammation-via-nlrp3-inflammasome-in-mouse-models-of-obesity
#12
Ji Hye Han, Hanho Shin, Jun Gi Rho, Jung-Eun Kim, Dong Hwee Son, Juhwan Yoon, Yong Jae Lee, Jung-Hyuck Park, Byung Jeong Song, Chang-Sik Choi, Seul Gi Yoon, Il Yong Kim, Eun Kyung Lee, Je Kyung Seong, Ki Woo Kim, Wook Kim
AIMS: Cannabinoid 1 receptor (CB1R) antagonists have been shown to improve insulin resistance and the associated metabolic abnormalities, but their therapeutic development was discontinued due to neuropsychiatric side effects. This study evaluated AJ5018 as the peripherally restricted CB1R antagonist, synthesized by modifying the structure of its brain-penetrant parent compound rimonabant, and analyzed the metabolic parameters and adipose tissue inflammation via NLRP3 inflammasome following chronic treatment of mouse models of obesity with AJ5018...
May 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29740932/antagonizing-peroxisome-proliferator-activated-receptor-%C3%AE-facilitates-m1-to-m2-shift-of-microglia-by-enhancing-autophagy-via-the-lkb1-ampk-signaling-pathway
#13
Juan Ji, Teng-Fei Xue, Xu-Dong Guo, Jin Yang, Ruo-Bing Guo, Juan Wang, Ji-Ye Huang, Xiao-Jie Zhao, Xiu-Lan Sun
Microglia-mediated neuroinflammation plays a dual role in various brain diseases due to distinct microglial phenotypes, including deleterious M1 and neuroprotective M2. There is growing evidence that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone prevents lipopolysaccharide (LPS)-induced microglial activation. Here, we observed that antagonizing PPARγ promoted LPS-stimulated changes in polarization from the M1 to the M2 phenotype in primary microglia. PPARγ antagonist T0070907 increased the expression of M2 markers, including CD206, IL-4, IGF-1, TGF-β1, TGF-β2, TGF-β3, G-CSF, and GM-CSF, and reduced the expression of M1 markers, such as CD86, Cox-2, iNOS, IL-1β, IL-6, TNF-α, IFN-γ, and CCL2, thereby inhibiting NFκB-IKKβ activation...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29737371/efficacy-and-safety-of-interleukin-1-antagonists-in-rheumatoid-arthritis-a-systematic-review-and-meta-analysis
#14
REVIEW
Shekoufeh Nikfar, Parisa Saiyarsarai, Bereket Molla Tigabu, Mohammad Abdollahi
Rheumatoid arthritis patients have a high level of pro-inflammatory interleukin-1. Augmenting the blockade of interleukin-1 receptors by external interleukin-1 receptor antagonist modifies the progression of the disease. Therefore, the aim of this study was to evaluate the clinical efficacy and safety of interleukin-1 receptor antagonist (anakinra) in the treatment of rheumatoid arthritis. Clinical trials and extension studies that compared anakinra with placebo or other medications were included. Electronic bibliographic databases: PubMed, Scopus, and Web of Sciences were searched from inception to November 2017...
May 8, 2018: Rheumatology International
https://www.readbyqxmd.com/read/29735520/identification-of-specific-components-of-the-eicosanoid-biosynthetic-and-signaling-pathway-involved-in-pathological-inflammation-during-intra-abdominal-infection-with-candida-albicans-and-staphylococcus-aureus
#15
Mélanie A C Ikeh, Paul L Fidel, Mairi C Noverr
Polymicrobial intra-abdominal infections (IAI) are a significant cause of morbidity and mortality, particularly when fungal pathogens are involved. Our experimental murine model of IAI involving intra-peritoneal inoculation of Candida albicans and Staphylococcus aureus results in synergistic lethality (∼80%) due to exacerbated inflammation. Monomicrobial infection results in no mortality despite similar microbial burden and dissemination as a co-infection. In the co-infection model, the immunomodulatory eicosanoid, prostaglandin E2 (PGE2 ) was determined to be necessary and sufficient to induce mortality implicating PGE2 as the central mediator of the amplified inflammatory response...
May 7, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29731737/lh-21-a-peripheral-cannabinoid-receptor-1-antagonist-exerts-favorable-metabolic-modulation-including-antihypertensive-effect-in-kkay-mice-by-regulating-inflammatory-cytokines-and-adipokines-on-adipose-tissue
#16
Ziqi Dong, Hui Gong, Yadan Chen, Hong Wu, Jun Wu, Yinghong Deng, Xinmao Song
Patients with obesity are susceptible to hypertension and diabetes. Over-activation of cannabinoid receptor 1 (CB1 R) in adipose tissue is proposed in the pathophysiology of metabolic disorders, which led to the metabolic dysfunction of adipose tissue and deregulated production and secretion of adipokines. In the current study, we determined the impact of LH-21, a representative peripheral CB1 R antagonist, on the obesity-accompanied hypertension and explored the modulatory action of LH-21 on the adipose tissue in genetically obese and diabetic KKAy mice...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29731098/efficacy-and-safety-of-induction-therapy-in-kidney-transplantation-a-network-meta-analysis
#17
S D Hwang, J H Lee, S W Lee, K-M Park, J K Kim, M-J Kim, J H Song
BACKGROUND: Rejection and infection can occur after kidney transplantation and are important factors in preserving graft kidney function. The use of immunosuppressant agents in transplantation is therefore important, and the question of which induction therapy should be used as an immunosuppressant is controversial. OBJECTIVE: The goal of this study was to assess the comparative benefits and harms of various maintenance immunosuppressive induction agents in adults undergoing kidney transplantation by using a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29730395/profiling-inflammatory-signatures-of-schizophrenia-a-cross-sectional-and-meta-analysis-study
#18
Dorota Frydecka, Małgorzata Krzystek-Korpacka, Alba Lubeiro, Filip Stramecki, Bartłomiej Stańczykiewicz, Jan Aleksander Beszłej, Patryk Piotrowski, Kamila Kotowicz, Monika Szewczuk-Bogusławska, Edyta Pawlak-Adamska, Błażej Misiak
We aimed to profile a broad panel of inflammatory markers in patients with schizophrenia and healthy controls. Additionally, we performed a meta-analysis of chemokine alterations that have not been subjected to quantitative synthesis so far. We recruited 78 patients with schizophrenia and 78 healthy controls, and measured inflammatory markers using the Luminex technology. After adjustment for multiple testing, we found elevated levels of interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, interferon-γ, eotaxin-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor with two B subunits (PDGF-BB), macrophage inflammatory protein (MIP)-1α, MIP-1β, vascular endothelial growth factor A (VEGF-A) and RANTES in multiple-episode schizophrenia (MES) patients...
May 3, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29724880/-il-10ra-mutation-as-a-risk-factor-of-severe-influenza-associated-encephalopathy-a-case-report
#19
Takashi Ishige, Yoshiko Igarashi, Reiko Hatori, Maiko Tatsuki, Yoji Sasahara, Takumi Takizawa, Hirokazu Arakawa
Influenza-associated encephalitis and encephalopathy (IAE) is a severe complication of influenza infection with high morbidity and mortality. We present the case of a patient with IL-10RA mutation who developed encephalopathy after influenza infection. A 10-day-old boy developed recurrent fever and anal fistula. Growth failure gradually became apparent. He had been treated with antibiotics and elemental nutrition. However, the patient did not respond to the treatments. At 11 months, he suddenly developed shock with encephalopathy and multiple organ failures...
May 3, 2018: Pediatrics
https://www.readbyqxmd.com/read/29724623/mechanism-of-interleukin-1-receptor-antagonist-protection-against-myocardial-ischaemia-reperfusion-induced-injury
#20
Wenhao Qian, Changyun Zhao, Dongye Li, Rui Dai
BACKGROUND: New therapeutic targets are required for ischaemic heart disease; our study was designed to assess the theoretical foundation and experimental basis underlying the use of a new anticytokine agent, interleukin-1 receptor antagonist (IL-1ra), in this setting. AIM: To investigate the cardioprotective properties of IL-1ra in terms of inhibition of apoptosis and improvement in systolic and diastolic functions of ischaemia/reperfusion (I/R)-injured cardiomyocytes, via a reduction in the inositol 1,4,5-trisphosphate (IP3) receptor-mediated Ca2+ overload induced by myocardial I/R injury...
April 30, 2018: Archives of Cardiovascular Diseases
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