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Interleukin 1 receptor antagonist

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https://www.readbyqxmd.com/read/28324042/interleukin-1-antagonism-decreases-cortisol-levels-in-obese-individuals
#1
Sandrine Andrea Urwyler, Philipp Schuetz, Fahim Ebrahimi, Marc Y Donath, Mirjam Christ-Crain
Context: Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH). Objective: We hypothesised that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal (HPA) axis, leading to decreased cortisol levels. Design and participants: In this prospective intervention study we included 73 patients with obesity (BMI >30kg/m2) and at least one additional feature of the metabolic syndrome...
February 20, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28322132/therapeutically-targeting-the-inflammasome-product-in-a-chimeric-model-of-endometriosis-related-surgical-adhesions
#2
Meredith M Stocks, Marta A Crispens, Tianbing Ding, Shilpa Mokshagundam, Kaylon L Bruner-Tran, Kevin G Osteen
Development of adhesions commonly occurs in association with surgery for endometriosis. Even in the absence of surgery, women with endometriosis appear to be at an enhanced risk of developing adhesions. In the current study, we utilized a chimeric mouse model of experimental endometriosis in order to examine the role of inflammasome activation in the development of postsurgical adhesions. Mice were randomized to receive peritoneal injections of human endometrial tissue fragments or endometrial tissue conditioned media (CM) from women with or without endometriosis 16 hours after ovariectomy and placement of an estradiol-releasing silastic capsule...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#3
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28321024/the-growth-hormone-secretagogue-hexarelin-protects-rat-cardiomyocytes-from-in-vivo-ischemia-reperfusion-injury-through-interleukin-1-signaling-pathway
#4
Jiannan Huang, Yi Li, Juan Zhang, Yusheng Liu, Qinghua Lu
Hexarelin, a synthetic growth hormone-releasing peptide, has been proven to possess cardioprotective actions through its binding to the growth hormone secretagogue receptor (GHSR) 1a and the non-GHSR receptor CD36. However, its effect on myocardial ischemia/reperfusion (I/R) injury has not been fully clarified in vivo. We aimed to determine whether hexarelin treatment could protect cardiomyocytes from I/R injury and to examine the underlying mechanisms. In vivo hearts of male SD rats underwent 30 minutes of ischemia by left coronary artery ligation followed by reperfusion...
March 17, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28299830/repeated-water-avoidance-stress-induces-visceral-hypersensitivity-role-of-il-1-il-6-and-peripheral-corticotropin-releasing-factor
#5
Tsukasa Nozu, Saori Miyagishi, Rintaro Nozu, Kaoru Takakusaki, Toshikatsu Okumura
BACKGROUND AND AIM: Repeated water avoidance stress (WAS) induces visceral hypersensitivity. Additionally, it is also known to activate corticotropin-releasing factor (CRF), mast cells and pro-inflammatory cytokines systems, but their precise roles on visceral sensation have not been determined definitely. The aim of the study was to explore this issue. METHODS: Abdominal muscle contractions induced by colonic balloon distention, i.e. visceromotor response (VMR) was detected electrophysiologically in conscious rats...
March 15, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28298024/reduction-of-inflammation-after-administration-of-interleukin-1-receptor-antagonist-following-aneurysmal-subarachnoid-hemorrhage-results-of-the-subcutaneous-interleukin-1ra-in-sah-scil-sah-study
#6
James Galea, Kayode Ogungbenro, Sharon Hulme, Hiren Patel, Sylvia Scarth, Margaret Hoadley, Karen Illingworth, Catherine J McMahon, Nikolaos Tzerakis, Andrew T King, Andy Vail, Stephen J Hopkins, Nancy Rothwell, Pippa Tyrrell
OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular event with long-term morbidity and mortality. Patients who survive the initial bleeding are likely to suffer further early brain injury arising from a plethora of pathological processes. These may result in a worsening of outcome or death in approximately 25% of patients and may contribute to longer-term cognitive dysfunction in survivors. Inflammation, mediated by the cytokine interleukin-1 (IL-1), is an important contributor to cerebral ischemia after diverse forms of brain injury, including aSAH...
February 24, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28294424/therapeutic-regulation-of-systemic-inflammation-in-xenograft-recipients
#7
Hayato Iwase, Hong Liu, Tao Li, Zhongquiang Zhang, Bingsi Gao, Hidetaka Hara, Martin Wijkstrom, Cassandra Long, Ryan Saari, David Ayares, David K C Cooper, Mohamed B Ezzelarab
Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients...
March 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28293435/interleukin-1-receptor-antagonist-and-interleukin-4-genes-variable-number-tandem-repeats-are-associated-with-adiposity-in-malaysian-subjects
#8
Yung-Yean Kok, Hing-Huat Ong, Yee-How Say
Interleukin-1 receptor antagonist (IL1RA) intron 2 86 bp repeat and interleukin-4 (IL4) intron 3 70 bp repeat are variable number tandem repeats (VNTRs) that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes...
2017: Journal of Obesity
https://www.readbyqxmd.com/read/28283331/the-role-of-foxo1-in-interleukin-1%C3%AE-induced-autostimulation-in-retina-endothelial-cells-and-retinas-of-diabetic-rats
#9
Lina Wu, Feng Guo, Yang Wu, Qingzhu Wang, Xiaojun Ma, Yanyan Zhao, Guijun Qin
Diabetic retinopathy is a chronic, low-grade inflammatory disease. The present study aimed to investigate the effect of forkhead transcription factor O1 (FoxO1) expression on interleukin-1β (IL-1β)-induced autostimulation, both in vitro in human retina microvascular endothelial cells (HRMECs), and in vivo in retinas isolated from streptozotocin-induced diabetic rats. High-glucose (HG) and recombinant IL-1β treatment were both shown to increase the expression of FoxO1 and IL-1β in HRMECs in a dose-dependent manner...
March 7, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28275350/blockade-of-p2x4-receptors-inhibits-neuropathic-pain-related-behavior-by-preventing-mmp-9-activation-and-consequently-pronociceptive-interleukin-release-in-a-rat-model
#10
Agnieszka M Jurga, Anna Piotrowska, Wioletta Makuch, Barbara Przewlocka, Joanna Mika
Neuropathic pain is still an extremely important problem in today's medicine because opioids, which are commonly used to reduce pain, have limited efficacy in this type of pathology. Therefore, complementary therapy is needed. Our experiments were performed in rats to evaluate the contribution of the purinergic system, especially P2X4 receptor (P2X4R), in the modulation of glia activation and, consequently, the levels of nociceptive interleukins after chronic constriction injury (CCI) of the right sciatic nerve, a rat model of neuropathic pain...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28260057/inhibition-of-triggering-receptor-expressed-on-myeloid-cells-1-ameliorates-experimental-autoimmune-neuritis
#11
Xiaoliang Zhou, Yanli Wang, Yuzhong Wang, Peter Cipriano, Bo Xiao, Wenbin Zhou
Experimental autoimmune neuritis (EAN) is a cluster of differentiation 4+ T helper 1 cell-mediated inflammatory demyelinating disease of the peripheral nervous system and serves as a useful animal model for Guillain‑Barré syndrome. Triggering receptor expressed on myeloid cells‑1 (TREM‑1) is an important receptor involved in sepsis and the innate inflammatory response. Linear plasmid 17 (LP 17) peptide is a competitive antagonist of TREM‑1. To investigate the role of TREM‑1 in EAN, 64 male Lewis rats were randomly divided into four groups: Normal saline, complete Freund's adjuvant, EAN and LP 17...
February 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28255166/capsaicin-prevents-degeneration-of-dopamine-neurons-by-inhibiting-glial-activation-and-oxidative-stress-in-the-mptp-model-of-parkinson-s-disease
#12
Young C Chung, Jeong Y Baek, Sang R Kim, Hyuk W Ko, Eugene Bok, Won-Ho Shin, So-Yoon Won, Byung K Jin
The effects of capsaicin (CAP), a transient receptor potential vanilloid subtype 1 (TRPV1) agonist, were determined on nigrostriatal dopamine (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The results showed that TRPV1 activation by CAP rescued nigrostriatal DA neurons, enhanced striatal DA functions and improved behavioral recovery in MPTP-treated mice. CAP neuroprotection was associated with reduced expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and reactive oxygen species/reactive nitrogen species from activated microglia-derived NADPH oxidase, inducible nitric oxide synthase or reactive astrocyte-derived myeloidperoxidase...
March 3, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28252571/interleukin-1-receptor-antagonist-polymorphism-and-birth-timing-pathway-analysis-among-african-american-women
#13
Shannon L Gillespie, Jeremy L Neal, Lisa M Christian, Laura A Szalacha, Donna O McCarthy, Pamela J Salsberry
BACKGROUND: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking...
March 2017: Nursing Research
https://www.readbyqxmd.com/read/28243146/p2y12-receptor-mediated-activation-of-spinal-microglia-and-p38mapk-pathway-contribute-to-cancer-induced-bone-pain
#14
Mingjuan Liu, Ming Yao, Hanqi Wang, Longsheng Xu, Ying Zheng, Bing Huang, Huadong Ni, Shijie Xu, Xuyan Zhou, Qingquan Lian
BACKGROUND: Cancer-induced bone pain (CIBP) is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent evidence has demonstrated that activation of microglial G-protein-coupled P2Y12 receptor (P2Y12R) and proinflammatory cytokine production play an important role in neuropathic pain generation and maintenance. However, whether P2Y12R is involved in CIBP remains unknown. METHODS: The purpose of this study was to investigate the role of P2Y12R in CIBP and its molecular mechanisms...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28242296/proteomic-and-histopathological-characterization-of-the-interface-between-oral-squamous-cell-carcinoma-invasion-fronts-and-non-cancerous-epithelia
#15
Tatsuya Abé, Satoshi Maruyama, Manabu Yamazaki, Bo Xu, Hamzah Babkair, Yoshimasa Sumita, Jun Cheng, Tadashi Yamamoto, Takashi Saku
Oral squamous cell carcinomas (SCCs) are frequently associated with pre-invasive lesions including carcinoma in-situ (CIS), and CISs further form lateral interfaces against surrounding normal or dysplastic epithelia (ND). At the interface where keratin (K) 17 positive (+) SCC/CIS cells are in contact with K13+ ND cells, "cell competition" must be evoked between two such different cell types. Thus, the aim of this study was to characterize the histopathology of the SCC/CIS-ND interface and to determine protein profiles around the interface by proteomics...
February 27, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28240322/influence-of-extracellular-zinc-on-m1-microglial-activation
#16
Youichirou Higashi, Takaaki Aratake, Shogo Shimizu, Takahiro Shimizu, Kumiko Nakamura, Masayuki Tsuda, Toshio Yawata, Tetuya Ueba, Motoaki Saito
Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30-60 μM ZnCl2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28236037/ppar%C3%AE-%C3%AE-antagonists-reverse-the-ameliorative-effects-of-osthole-on-hepatic-lipid-metabolism-and-inflammatory-response-in-steatohepatitic-rats
#17
Xi Zhao, Feng Wang, Ruijun Zhou, Zengyan Zhu, Meilin Xie
Our previous studies have indicated that osthole may ameliorate the hepatic lipid metabolism and inflammatory response in nonalcoholic steatohepatitic rats, but the underlying mechanisms remain unclear. This study aimed to determine whether the effects of osthole were mediated by the activation of hepatic peroxisome proliferator-activated receptor α/γ (PPARα/γ). A rat model with steatohepatitis was induced by orally feeding high-fat and high-sucrose emulsion for 6 weeks. These experimental rats were then treated with osthole (20 mg/kg), PPARα antagonist MK886 (1 mg/kg) plus osthole (20 mg/kg), PPARγ antagonist GW9662 (1 mg/kg) plus osthole (20 mg/kg) and MK886 (1 mg/kg) plus GW9662 (1 mg/kg) plus osthole (20 mg/kg) for 4 weeks...
February 25, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28230639/mammalian-target-of-rapamycin-inhibition-clinical-transplantation-liver
#18
Björn Nashan
The evidence base concerning use of mammalian target of rapamycin (mTOR) inhibitor therapy after liver transplantation is evolving rapidly, clarifying their benefits and disadvantages in different clinical scenarios. The H2304 trial showed that starting everolimus at 1 month posttransplant, with reduced tacrolimus, achieves a sustained improvement in renal function versus standard tacrolimus-based therapy, with at least equivalent immunosuppressive efficacy. Randomized studies evaluating early discontinuation of CNI therapy after introduction of an mTOR inhibitor consistently demonstrated a substantial improvement in renal function versus standard CNI therapy...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28223018/cerebral-ischemia-induced-elevation-of-hepatic-inflammatory-factors-accompanied-by-glucose-intolerance-suppresses-hypothalamic-orexin-a-mediated-vagus-nerve-activation
#19
Shinichi Harada, Yudai Nozaki, Wataru Matsuura, Yui Yamazaki, Shogo Tokuyama
Activation of vagus nerve exerts orexin-A (OXA)-mediated suppression of post-ischemic glucose intolerance and cerebral ischemic neuronal damage. Cerebral ischemia induces hepatic inflammatory factors and contributes to the development of hepatic insulin resistance by activating sympathetic nerves. However, it is not enough to understand whether OXA regulates these phenomena through activation of vagus nerve. In this study, we demonstrated that the involvement of OXA-induced activation of vagus nerve in the induction of hepatic inflammatory factors by cerebral ischemia...
April 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28219695/inhibitory-effects-of-dynorphin-3-14-on-the-lipopolysaccharide-induced-toll-like-receptor-4-signalling-pathway
#20
Siti Sarah Fazalul Rahiman, Michael Morgan, Paul Gray, Paul Nicholas Shaw, Peter John Cabot
Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells...
February 20, 2017: Peptides
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