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Il-1 receptor antagonist

Xiaoxing Kou, Xingtian Xu, Chider Chen, Maria Laura Sanmillan, Tao Cai, Yanheng Zhou, Claudio Giraudo, Anh Le, Songtao Shi
Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs...
March 14, 2018: Science Translational Medicine
Satyanarayana Achanta, Narendranath Reddy Chintagari, Marian Brackmann, Shrilatha Balakrishna, Sven-Eric Jordt
The skin is highly sensitive to the chemical warfare agent in mustard gas, sulfur mustard (SM) that initiates a delayed injury response characterized by erythema, inflammation and severe vesication (blistering). Although SM poses a continuing threat, used as recently as in the Syrian conflict, no mechanism-based antidotes against SM are available. Recent studies demonstrated that Transient Receptor Potential Ankyrin 1 (TRPA1), a chemosensory cation channel in sensory nerves innervating the skin, is activated by SM and 2-chloroethyl ethyl sulfide (CEES), an SM analog, in vitro, suggesting it may promote vesicant injury...
March 10, 2018: Toxicology Letters
Shayna E Thomas-Jardin, Mohammed S Kanchwala, Joan Jacob, Sana Merchant, Rachel K Meade, Nagham M Gahnim, Afshan F Nawas, Chao Xing, Nikki A Delk
BACKGROUND: In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance...
March 11, 2018: Prostate
Christian Herder, Andreas Schmitt, Florian Budden, André Reimer, Bernhard Kulzer, Michael Roden, Thomas Haak, Norbert Hermanns
BACKGROUND: Depressive disorders represent a frequent comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). Subclinical inflammation increases the risk of depressive symptoms in the general population, but the relationship appears complex and bidirectional, and longitudinal data from patients with diabetes are lacking. Therefore, this study aimed to analyse associations between changes in depressive symptoms and changes in biomarkers of inflammation in patients with T1D and T2D and to investigate the hypothesis that higher baseline levels of biomarkers of inflammation are related to a less pronounced reduction of depressive symptoms over time...
March 6, 2018: Psychoneuroendocrinology
Christian Herder, Andreas Schmitt, Florian Budden, André Reimer, Bernhard Kulzer, Michael Roden, Thomas Haak, Norbert Hermanns
Subclinical inflammation has been implicated in the development of depression, a common comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). This study aimed to characterise the relationships between biomarkers of inflammation and depressive symptoms in T1D and T2D. Biomarkers of inflammation were measured in serum of participants with elevated depressive symptoms and T1D (n = 389, mean age 38 years, diabetes duration 15 ± 11 years) or T2D (n = 204, mean age 56 years, diabetes duration 13 ± 8 years)...
March 9, 2018: Translational Psychiatry
Minke H T Hartman, Hilde E Groot, Irene Mateo Leach, Jacco C Karper, Pim van der Harst
Many cytokines are currently under investigation as potential target to improve cardiac function and outcome in the setting of acute myocardial infarction (MI) or chronic heart failure (HF). Here we aim to provide a translational overview of cytokine inhibiting therapies tested in experimental models and clinical studies. In various experimental studies, inhibition of interleukin-1 (IL-1), -6 (IL-6), -8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), CC- and CXC chemokines, and tumor necrosis factor-α (TNF-α) had beneficial effects on cardiac function and outcome...
February 15, 2018: Trends in Cardiovascular Medicine
Andrea Cecilia Parrado, Luciana Soledad Salaverry, Franco Mauricio Mangone, Carolina Eugenia Apicella, Teresa Gentile, Andrea Canellada, Estela Beatriz Rey-Roldán
OBJECTIVE: Dopamine is an immunomodulatory neurotransmitter. In the skin, keratinocytes and macrophages produce proinflammatory cytokines and metalloproteinases (MMPs) which participate in wound healing. These cells have a catecholaminergic system that modulates skin pathophysiologic processes. We have demonstrated that dopamine modulates cytokine production in keratinocytes via dopaminergic and adrenergic receptors (ARs). The aim of this study was to evaluate the effect of dopamine and its interaction with β-ARs in human HaCaT keratinocytes and THP-1 macrophages...
March 7, 2018: Neuroimmunomodulation
Kazuhiko Matsuo, Daisuke Nagakubo, Yuhei Komori, Shun Fujisato, Natsumi Takeda, Mizuki Kitamatsu, Keiji Nishiwaki, Ying-Shu Quan, Fumio Kamiyama, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama
Atopic dermatitis (AD) is a chronic inflammatory skin disease involving Th2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in AD still remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute AD-like skin lesions in BALB/c mice, a strain prone to Th2 responses, that were characterized by (1) increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions, (2) elevated levels of total and ovalbumin-specific IgE in the sera, and (3) increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions...
March 3, 2018: Journal of Investigative Dermatology
Zhi-Yin Lou, Jie Cheng, Xiao-Rong Wang, Yong-Fei Zhao, Jing Gan, Guo-Yu Zhou, Zhen-Guo Liu, Bao-Guo Xiao
Cannabinoid 1 receptor (CB1 R) regulates the neuro-inflammatory and neurodegenerative damages of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1 R inhibition exerts inflammatory effects is still unclear. Here, we explored the cellular and molecular mechanisms of CB1 R in the treatment of EAE by using a specific and selective CB1 R antagonist SR141716A. Our study demonstrated that SR141716A accelerated the clinical onset and development of EAE, accompanied by body weight loss...
April 15, 2018: Journal of Neuroimmunology
Carlene Petes, Mélissa K Mariani, Yawen Yang, Nathalie Grandvaux, Katrina Gee
Interleukin (IL)-30, the IL-27p28 subunit of the heterodimeric cytokine IL-27, acts as an antagonist of IL-27 and IL-6 signaling in murine cells via glycoprotein 130 (gp130) receptor and additional binding partners. Thus far, functions of IL-30 have not been fully elucidated in human cells. We demonstrate that like IL-27, IL-30 upregulated TLR4 expression to enhance lipopolysaccharide-induced TNF-α production in human monocytes; however, these IL-30-mediated activities did not reach the same levels of cytokine induction compared to IL-27...
2018: Frontiers in Immunology
Sílvia Castany, Georgia Gris, José Miguel Vela, Enrique Verdú, Pere Boadas-Vaello
Sigma-1 receptor (σ1 R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) - a model of central neuropathic pain. The modulatory effect of σ1 R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed...
March 1, 2018: Scientific Reports
Pablo Torres-Vergara, Jeffrey Penny
OBJECTIVES: The effects of anti-inflammatory glucocorticoids dexamethasone (DX) and hydrocortisone (HC), pro-inflammatory cytokine interleukin-1β (IL-1β) and dietary long-chain polyunsaturated fatty acids (PUFAs) on expression and activity of the ATP-binding cassette transporter P-glycoprotein (P-GP) were studied in porcine brain endothelial cells (PBECs). METHODS: Primary PBECs were treated for 24 h with glucocorticoids, IL-1β and long-chain PUFAs. P-GP activity was determined by measuring intracellular calcein accumulation and P-GP expression by Western blotting...
March 1, 2018: Journal of Pharmacy and Pharmacology
Nishkantha Arulkumaran, Marije L Sixma, Sean Pollen, Elias Ceravola, Elisa Jentho, Maria Prendecki, Paul S Bass, Frederick W K Tam, Robert J Unwin, Mervyn Singer
Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid-resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this purinergic receptor to renal dysfunction in sepsis. Six and 24 h time-points were chosen to represent early and established sepsis, respectively. A selective P2X7 receptor antagonist (A-438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis...
March 2018: Physiological Reports
Cui Li, Yuan-Yuan Liu, Gui-Qiu Zhao, Jing Lin, Cheng-Ye Che, Nan Jiang, Na Li, Jie Zhang, Kun He, Xu-Dong Peng
AIM: To investigate the anti-inflammatory role of vasoactive intestinal peptide (VIP) in Aspergillus fumigatus ( A. fumigatus ) ketatitis. METHODS: Expression of VIP was tested by polymerase chain reaction (PCR) in C57BL/6 and BALB/c normal and A. fumigatus infected corneas. C57BL/6 mice were pretreated with recombinant (r) VIP, while BALB/c mice were pretreated with VIP antagonist, and then infected with A. fumigatus . Clinical score was recorded. Expression of pro- and anti-inflammatory cytokines, toll-like receptor 4 (TLR4), lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and neutrophil infiltration were tested by PCR, enzyme-linked immunosorbent assay (ELISA), and myeloperoxidase (MPO) assay...
2018: International Journal of Ophthalmology
Kijun Lee, Narae Park, Hyerin Jung, Yeri Alice Rim, Yoojun Nam, Jennifer Lee, Sung-Hwan Park, Ji Hyeon Ju
Human bone marrow-derived mesenchymal stem cells (MSCs) have been observed to inhibit arthritis in experimental animal models such as collagen-induced arthritis. However, the exact anti-inflammatory mechanisms remain poorly understood. Interleukin-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine produced by immune and stromal cells. We postulated that MSCs could produce IL-1Ra and attenuate experimental arthritis. In this study, 5x106 MSCs were injected into the peritoneal cavity of IL-1Ra knockout (IL-1RaKO) mice...
2018: PloS One
M N Karpenko, A A Vasilishina, E A Gromova, Z M Muruzheva, A Bernadotte
Several parameters representing the clinical diversity of Parkinson's disease (PD), including severity, phenotypes, cognitive decline, anxiety and depression were analyzed to examine the link with interleukin-1β (IL-1β), the interleukin-1 receptor antagonist (IL-1RA), IL-6, IL-10, and tumor necrosis factor-α (TNFα) and also to determine the relationship between levels of these factors in serum and cerebrospinal fluid (CSF). Significantly elevated serum IL-1β and IL-6 and reduced IL-1RA levels were found in the PD group...
February 19, 2018: Cellular Immunology
Yingjie Qi, Igor Klyubin, A Claudio Cuello, Michael J Rowan
Pro-inflammatory mechanisms have recently emerged as an important component of early Alzheimer's disease (AD) pathogenesis. A particularly attractive therapeutic strategy is to selectively prevent the disruptive effects of activation of the innate immune system in the brain at an early transitional stage by reducing the production or directly neutralizing pro-inflammatory cytokines, in particular IL-1β and TNF-α. Here we tested their in vivo effects on synaptic plasticity deficits, which provide sensitive and robust measures of synaptic failure, in a rat model of AD amyloidosis...
February 22, 2018: Neurobiology of Disease
William M Armstead, Hugh Hekierski, Philip Pastor, Serge Yarovoi, Abd Al-Roof Higazi, Douglas B Cines
The sole FDA-approved drug treatment for ischemic stroke is tissue-type plasminogen activator (tPA). However, upregulation of JNK mitogen-activated protein kinase (MAPK) and endothelin 1 (ET-1) by tPA after stroke contributes to impaired cerebrovascular autoregulation. Wild-type (wt) tPA can bind to the lipoprotein-related receptor (LRP), which mediates vasodilation, or NMDA receptors (NMDA-Rs), exacerbating vasoconstriction. Elevations in IL-6, a marker of inflammation that accompanies stroke, are reported to be an adverse prognostic factor...
February 23, 2018: Translational Stroke Research
Yun Zhang, Garth L Warnock, Ziliang Ao, Yoo Jin Park, Nooshin Safikhan, Aziz Ghahary, Lucy Marzban
Amyloid formation in the pancreatic islets due to aggregation of human islet amyloid polypeptide (hIAPP) contributes to reduced β-cell mass and function in type 2 diabetes (T2D) and islet transplantation. Protein kinase B (PKB) signaling plays a key role in the regulation of β-cell survival, function and proliferation. In this study, we used human and hIAPP-expressing transgenic mouse islets in culture as two ex vivo models of human islet amyloid formation to: 1. Investigate the effects of amyloid formation on PKB phosphorylation in primary islet β-cells; 2...
2018: PloS One
Fernanda Maria Martins, Aletéia de Paula Souza, Paulo Ricardo Prado Nunes, Márcia Antoniazi Michelin, Eddie Fernando Candido Murta, Elisabete Aparecida Mantovani Rodrigues Resende, Erick Prado de Oliveira, Fábio Lera Orsatti
OBJECTIVE: This study compared the effects of 12 weeks of high-intensity interval body weight training (HIBWT) with combined training (COMT; aerobic and resistance exercises on body composition, a 6-minute walk test (6MWT; physical performance), insulin resistance (IR) and inflammatory markers in postmenopausal women (PW) at high risk of type 2 diabetes mellitus (TDM2). METHODS: In this randomized controlled clinical study, 16 PW at high risk of TDM2 were randomly allocated into two groups: HIBWT (n = 8) and COMT (n = 8)...
February 19, 2018: Experimental Gerontology
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