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Il-1 receptor antagonist

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https://www.readbyqxmd.com/read/28205525/testicular-activin-and-follistatin-levels-are-elevated-during-the-course-of-experimental-autoimmune-epididymo-orchitis-in-mice
#1
Nour Nicolas, Vera Michel, Sudhanshu Bhushan, Eva Wahle, Susan Hayward, Helen Ludlow, David M de Kretser, Kate L Loveland, Hans-Christian Schuppe, Andreas Meinhardt, Mark P Hedger, Monika Fijak
Experimental autoimmune epididymo-orchitis (EAEO) is a model of chronic inflammation, induced by immunisation with testicular antigens, which reproduces the pathology of some types of human infertility. Activins A and B regulate spermatogenesis and steroidogenesis, but are also pro-inflammatory, pro-fibrotic cytokines. Expression of the activins and their endogenous antagonists, inhibin and follistatin, was examined in murine EAEO. Adult untreated and adjuvant-treated control mice showed no pathology. All mice immunised with testis antigens developed EAEO by 50 days, characterised by loss of germ cells, immune cell infiltration and fibrosis in the testis, similar to biopsies from human inflamed testis...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28204809/ketamine-suppresses-the-substance-p-induced-production-of-il-6-and-il-8-by-human-u373mg-glioblastoma-astrocytoma-cells
#2
Keisuke Yamaguchi, Seiichiro Kumakura, Taisuke Murakami, Akimasa Someya, Eiichi Inada, Isao Nagaoka
The neuropeptide substance P (SP) is an important mediator of neurogenic inflammation within the central and peripheral nervous systems. SP has been shown to induce the expression of pro-inflammatory cytokines implicated in the pathogenesis of several disorders of the human brain via the neurokinin-1 receptor (NK-1R). Ketamine, an intravenous anesthetic agent, functions as a competitive antagonist of the excitatory neurotransmission N-methyl-D‑aspartate (NMDA) receptor, and also antagonizes the NK-1R by interfering with the binding of SP...
February 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203105/association-of-fatigue-and-depression-with-circulating-levels-of-proinflammatory-cytokines-and-epidermal-growth-factor-receptor-ligands-a-correlative-study-of-a-placebo-controlled-fatigue-trial
#3
Tyvin Rich, Fengmin Zhao, Ricardo A Cruciani, David Cella, Judith Manola, Michael J Fisch
CONTEXT: The biology of fatigue and depression in cancer patients is poorly understood. Hypotheses regarding cytokines and growth factors related to sickness behavior and disruption of circadian signaling have been proposed. OBJECTIVES: We prospectively examined proinflammatory cytokines (e.g., sickness behavior model) and epidermal growth factor receptor (EGFR) ligands (e.g., circadian disruption model) in the serum of cancer patients enrolled in a clinical trial testing levocarnitine for fatigue...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28202084/aprepitant-limits-in-vivo-neuroinflammatory-responses-in-a-rhesus-model-of-lyme-neuroborreliosis
#4
Alejandra N Martinez, Amanda R Burmeister, Geeta Ramesh, Lara Doyle-Meyers, Ian Marriott, Mario T Philipp
BACKGROUND: Substance P (SP) is produced at high levels in the central nervous system (CNS), and its target receptor, neurokinin 1 receptor (NK-1R), is expressed by glia and leukocytes. This tachykinin functions to exacerbate inflammatory responses at peripheral sites. Moreover, SP/NK-1R interactions have recently been associated with severe neuroinflammation and neuronal damage. We have previously demonstrated that NK-1R antagonists can limit neuroinflammatory damage in a mouse model of bacterial meningitis...
February 15, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28193826/the-nlrp3-inflammasome-has-a-critical-role-in-peritoneal-dialysis-related-peritonitis
#5
Nicolas Hautem, Johann Morelle, Amadou Sow, Cyril Corbet, Olivier Feron, Eric Goffin, François Huaux, Olivier Devuyst
Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1β The NLRP3 inflammasome is a caspase-1-activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1β The potential roles of the NLRP3 inflammasome and IL-1β in the peritoneal membrane during acute peritonitis have not been investigated...
February 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28193225/the-active-metabolite-of-leflunomide-a77-1726-attenuates-inflammatory-arthritis-in-mice-with-spontaneous-arthritis-via-induction-of-heme-oxygenase-1
#6
Su-Jin Moon, Eun-Kyung Kim, Joo Yeon Jhun, Hee Jin Lee, Weon Sun Lee, Sang-Hi Park, Mi-La Cho, Jun-Ki Min
BACKGROUND: Leflunomide is a low-molecular-weight compound that is widely used in the treatment of rheumatoid arthritis. Although leflunomide is thought to act through the inhibition of the de novo pyrimidine synthesis, the molecular mechanism of the drug remains largely unknown. We investigated the antiarthritis effects and mechanisms of action of the active metabolite of leflunomide, A77 1726, in interleukin-1 receptor antagonist-knockout (IL-1Ra-KO) mice. METHODS: 14- to 15-week-old male IL-1Ra-KO mice were treated with 10 or 30 mg/kg A77 1726 via intraperitoneal injection three times per week for 6 weeks...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28191908/il-1beta-induces-thymic-stromal-lymphopoietin-and-an-atopic-dermatitis-like-phenotype-in-reconstructed-healthy-human-epidermis
#7
Marine Bernard, Cédric Carrasco, Léo Laoubi, Béatrice Guiraud, Aurore Rozières, Catherine Goujon, Hélène Duplan, Sandrine Bessou-Touya, Jean-François Nicolas, Marc Vocanson, Marie-Florence Galliano
Atopic dermatitis (AD) is a common skin inflammatory disease characterized by the production of thymic stromal lymphopoietin (TSLP) and a marked TH 2 polarization. Recent studies suggest that IL-1β contributes to the development of AD skin inflammation. Here, we have investigated the impact of IL-1β signalling on the epidermal homeostasis of both healthy subjects and AD patient [with functional filaggrin (FLG) alleles] with particular attention to TSLP production and keratinocyte differentiation. In healthy reconstructed human epidermis (RHE), IL-1β promoted: (i) a robust secretion of TSLP in an NFkB-dependant manner and (ii) a significant decrease in the expression of filaggrin and other proteins of the epidermal differentiation complex...
February 13, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28187038/minocycline-prevents-the-impairment-of-hippocampal-long-term-potentiation-in-the-septic-mouse
#8
Koji Hoshino, Mineji Hayakawa, Yuji Morimoto
Sepsis-associated encephalopathy is a major complication during sepsis, and an effective treatment remains unknown. Although minocycline (MINO) has neuroprotective effects and is an attractive candidate for treating sepsis-associated encephalopathy, the effect of MINO on synaptic plasticity during sepsis is still unclear. In the present study, we investigated the effects of MINO on long-term potentiation (LTP) in the hippocampus in a cecal ligation and puncture (CLP) mouse model. We divided mice into 4 groups; (1) sham + vehicle, (2) sham + MINO (60 mg/kg, i...
February 9, 2017: Shock
https://www.readbyqxmd.com/read/28179433/il-36-signaling-facilitates-activation-of-the-nlrp3-inflammasome-and-il-23-il-17-axis-in-renal-inflammation-and-fibrosis
#9
Hsi-Hua Chi, Kuo-Feng Hua, Yu-Chuan Lin, Ching-Liang Chu, Chih-Yu Hsieh, Yu-Juei Hsu, Shuk-Man Ka, Yu-Ling Tsai, Feng-Cheng Liu, Ann Chen
IL-36 cytokines are proinflammatory and have an important role in innate and adaptive immunity, but the role of IL-36 signaling in renal tubulointerstitial lesions (TILs), a major prognostic feature of renal inflammation and fibrosis, remains undetermined. In this study, increased IL-36α expression detected in renal biopsy specimens and urine samples from patients with renal TILs correlated with renal function impairment. We confirmed the increased expression of IL-36α in the renal tubular epithelial cells of a mouse model of unilateral ureteral obstruction (UUO) and related cell models using mechanically induced pressure, oxidative stress, or high mobility group box 1...
February 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28174259/proinflammatory-cytokines-predict-the-incidence-and-progression-of-distal-sensorimotor-polyneuropathy-kora-f4-ff4-study
#10
Christian Herder, Julia M Kannenberg, Cornelia Huth, Maren Carstensen-Kirberg, Wolfgang Rathmann, Wolfgang Koenig, Margit Heier, Sonja Püttgen, Barbara Thorand, Annette Peters, Michael Roden, Christa Meisinger, Dan Ziegler
OBJECTIVE: Experimental and epidemiological studies have implicated inflammatory processes in the pathogenesis of distal sensorimotor polyneuropathy (DSPN), but prospective studies are lacking. We hypothesized that biomarkers of inflammation predict the development and progression of DSPN in a population-based cohort. RESEARCH DESIGN AND METHODS: This study was based on participants aged 62-81 years from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort, with a mean follow-up of 6...
February 7, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28168403/carbon-monoxide-releasing-molecule-3-improves-myocardial-function-in-mice-with-sepsis-by-inhibiting-nlrp3-inflammasome-activation-in-cardiac-fibroblasts
#11
Wenbo Zhang, Aibin Tao, Ting Lan, Gediminas Cepinskas, Raymond Kao, Claudio M Martin, Tao Rui
The NLRP3 inflammasome is an intracellular multiple-protein complex that controls the maturation and release of interleukin (IL)-1β and IL-18. Endogenous carbon monoxide (CO) is anti-inflammatory. The aim of this study was to assess the effects/mechanisms of CO-releasing molecule-3 (CORM-3)-dependent modulation of the NLRP3 inflammasome in cardiac fibroblasts (CF) and its effect on myocardial function in sepsis. CF were treated with CORM-3 or inactive CORM-3 (iCORM-3) before NLRP3 inflammasome priming with lipopolysaccharides (LPS) or following activation with adenosine triphosphate (ATP)...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28167912/c5a-regulates-il-1%C3%AE-production-and-leukocyte-recruitment-in-a-murine-model-of-monosodium-urate-crystal-induced-peritonitis
#12
Hanif J Khameneh, Adrian W S Ho, Federica Laudisi, Heidi Derks, Matheswaran Kandasamy, Baalasubramanian Sivasankar, Gim Gee Teng, Alessandra Mortellaro
Gouty arthritis results from the generation of monosodium urate (MSU) crystals within joints. These MSU crystals elicit acute inflammation characterized by massive infiltration of neutrophils and monocytes that are mobilized by the pro-inflammatory cytokine IL-1β. MSU crystals also activate the complement system, which regulates the inflammatory response; however, it is unclear whether or how MSU-mediated complement activation is linked to IL-1β release in vivo, and the various roles that might be played by individual components of the complement cascade...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28165339/mutations-in-sphingosine-1-phosphase-lyase-cause-nephrosis-with-ichthyosis-and-adrenal-insufficiency
#13
Svjetlana Lovric, Sara Goncalves, Heon Yung Gee, Babak Oskouian, Honnappa Srinivas, Won-Il Choi, Shirlee Shril, Shazia Ashraf, Weizhen Tan, Jia Rao, Merlin Airik, David Schapiro, Daniela A Braun, Carolin E Sadowski, Eugen Widmeier, Tilman Jobst-Schwan, Johanna Magdalena Schmidt, Vladimir Girik, Guido Capitani, Jung H Suh, Noëlle Lachaussée, Christelle Arrondel, Julie Patat, Olivier Gribouval, Monica Furlano, Olivia Boyer, Alain Schmitt, Vincent Vuiblet, Seema Hashmi, Rainer Wilcken, Francois P Bernier, A Micheil Innes, Jillian S Parboosingh, Ryan E Lamont, Julian P Midgley, Nicola Wright, Jacek Majewski, Martin Zenker, Franz Schaefer, Navina Kuss, Johann Greil, Thomas Giese, Klaus Schwarz, Vilain Catheline, Denny Schanze, Ingolf Franke, Yves Sznajer, Anne S Truant, Brigitte Adams, Julie Désir, Ronald Biemann, York Pei, Elisabet Ars, Nuria Lloberas, Alvaro Madrid, Vikas R Dharnidharka, Anne M Connolly, Marcia C Willing, Megan A Cooper, Richard P Lifton, Matias Simons, Howard Riezman, Corinne Antignac, Julie D Saba, Friedhelm Hildebrandt
Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase...
February 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28160128/blockade-of-the-kinin-b1-receptor-affects-the-cytokine-chemokine-profile-in-rat-brain-subjected-to-autoimmune-encephalomyelitis
#14
Karolina Podsiadło, Grzegorz Sulkowski, Beata Dąbrowska-Bouta, Lidia Strużyńska
Kinins are bioactive peptides which provide multiple functions, including critical regulation of the inflammatory response. Released during tissue injury, kinins potentiate the inflammation which represents a hallmark of numerous neurological disorders, including those of autoimmune origin such as multiple sclerosis (MS). In the present work, we assess the expression of B1 receptor (B1R) in rat brain during the course of experimental autoimmune encephalomyelitis (EAE) which is an animal model of MS. We apply pharmacological inhibition to investigate the role of this receptor in the development of neurological deficits and in shaping the cytokine/chemokine profile during the course of the disease...
February 3, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28155269/self-assembled-raspberry-like-core-satellite-nanoparticles-for-anti-inflammatory-protein-delivery
#15
Tingting Wang, Yaqin Tang, Xiao He, Ju Yan, Chenhui Wang, Xuli Feng
Functional proteins are very promising for protein therapeutics; however, effective delivery of therapeutic proteins remains challenging. Herein, we developed novel core/satellite nanoparticles by tethering therapeutic proteins to the core/shell polymeric particle surface through cucurbit[8]uril (CB[8])-mediated host-guest interactions. The effectiveness of the core/satellite nanoparticles as protein carrier was demonstrated through the intra-articular delivery of interleukin-1 receptor antagonist (IL-1Ra)...
February 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28154998/upregulated-expression-of-substance-p-sp-and-nk1r-in-eczema-and-sp-induced-mast-cell-accumulation
#16
Mengmeng Zhan, Wenjiao Zheng, Qijun Jiang, Zuotao Zhao, Zhiyun Wang, Junling Wang, Huiyun Zhang, Shaoheng He
Substance P (SP) was reported to be associated with eczema and acts as a potent skin mast cell secretagogue. However, little is known of its expression in inflammatory cells in eczema and its ability in induction of mast cell accumulation. In the present study, we investigated expression of SP and neurokinin-1 receptor (NK1R) on peripheral blood leukocytes and mast cells from patients with eczema and influence of SP on mast cell accumulation by using flow cytometry analysis, trans-epithelial cell migration assay and mouse peritoneal model...
February 2, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28153725/differences-in-the-effects-of-four-trpv1-channel-antagonists-on-lipopolysaccharide-induced-cytokine-production-and-cox-2-expression-in-murine-macrophages
#17
Yuki Ninomiya, Sei-Ichi Tanuma, Mitsutoshi Tsukimoto
Sepsis is a systemic inflammatory response syndrome triggered by lipopolysaccharide (LPS), an outer membrane component of gram-negative bacteria, and cytokine production via LPS-induced macrophage activation is deeply involved in its pathogenesis. Effective therapy of sepsis has not yet been established. However, it was reported that transient receptor potential vanilloid 1 (TRPV1) channel antagonist capsazepine (CPZ; a capsaicin analogue) attenuates sepsis in a murine model [Ang et al., PLoS ONE 6(9) (2011) e24535; J...
January 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28153540/involvement-of-peripheral-p2y1-receptors-and-potential-interaction-with-il-1-receptors-in-il-1%C3%AE-induced-thermal-hypersensitivity-in-rats
#18
Soon-Gu Kwon, Dae-Hyun Roh, Seo-Yeon Yoon, Sheu-Ran Choi, Hoon-Seong Choi, Ji-Young Moon, Suk-Yun Kang, Alvin J Beitz, Jang-Hern Lee
Although interleukin-1β (IL-1β) is a prototypical pro-inflammatory cytokine, the specific mechanisms underlying the role of its cognate receptor, the interleukin-1 receptor (IL-1R) in peripheral sensitization remain to be investigated. Since emerging evidence in the literature indicates that IL-1β can modulate membrane-bound receptors, we decided to examine the involvement of P2Y1 receptor (P2Y1R) in IL-1β induced pain and the potential interaction of P2Y1Rs and IL-1Rs in both naïve and carrageenan injected rats...
January 30, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28148737/antenatal-suppression-of-il-1-protects-against-inflammation-induced-fetal-injury-and-improves-neonatal-and-developmental-outcomes-in-mice
#19
Mathieu Nadeau-Vallée, Peck-Yin Chin, Lydia Belarbi, Marie-Ève Brien, Sheetal Pundir, Martin H Berryer, Alexandra Beaudry-Richard, Ankush Madaan, David J Sharkey, Alexis Lupien-Meilleur, Xin Hou, Christiane Quiniou, Alexandre Beaulac, Ines Boufaied, Amarilys Boudreault, Adriana Carbonaro, Ngoc-Duc Doan, Jean-Sebastien Joyal, William D Lubell, David M Olson, Sarah A Robertson, Sylvie Girard, Sylvain Chemtob
Preterm birth (PTB) is commonly accompanied by in utero fetal inflammation, and existing tocolytic drugs do not target fetal inflammatory injury. Of the candidate proinflammatory mediators, IL-1 appears central and is sufficient to trigger fetal loss. Therefore, we elucidated the effects of antenatal IL-1 exposure on postnatal development and investigated two IL-1 receptor antagonists, the competitive inhibitor anakinra (Kineret) and a potent noncompetitive inhibitor 101.10, for efficacy in blocking IL-1 actions...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28147432/peripheral-immune-system-adaptations-and-motivation-for-alcohol-in-non-dependent-problem-drinkers
#20
Verica Milivojevic, Emily Ansell, Christine Simpson, Kristen M Siedlarz, Rajita Sinha, Helen C Fox
BACKGROUND: Increasing evidence suggests that levels of pro-inflammatory and anti-inflammatory cytokines are dysfunctional in alcohol dependence. Moreover, some initial findings demonstrate that these adaptations in peripheral inflammation may contribute to motivation for alcohol and problem drinking via possible direct effects or the indirect effects of stress responsivity. Importantly, the role of pro-inflammatory and anti-inflammatory cytokines in the progression from healthy to problem drinking is not well understood...
February 1, 2017: Alcoholism, Clinical and Experimental Research
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