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TNF alpha antagonists

Sara Žigon-Branc, Ariana Barlič, Miomir Knežević, Matjaž Jeras, Gordana Vunjak-Novakovic
Inflammation plays a major role in progression of rheumatoid arthritis (RA), a disease treated with antagonists of tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß). New in vitro testing systems are needed to evaluate efficacies of new anti-inflammatory biological drugs, ideally in a patient-specific manner. To address this need, we studied microspheroids containing 10,000 human osteoarthritic primary chondrocytes (OACs) or chondrogenically differentiated mesenchymal stem cells (MSCs), obtained from three donors...
March 14, 2018: Biotechnology Progress
Katelyn F Woolridge, Patrick L Boler, Brian D Lee
Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction for which there is no standardized or consistently effective treatment. Due to a greater understanding of disease pathogenesis and the identification of tumor necrosis factor (TNF) α as a mediator of keratinocyte death, TNF-α antagonists have been used in the treatment of TEN. Specifically, infliximab and etanercept have been shown to be effective at halting disease progression. The objective of this study is to review published case reports and case series using anti-TNF-α medications in the treatment of TEN...
January 2018: Cutis; Cutaneous Medicine for the Practitioner
Xiaoyan Wang, Van A Villar, Andrew Tiu, Kiran K Upadhyay, Santiago Cuevas
Leptin is a pro-inflammatory cytokine secreted by the adipose tissue. Dopamine D2 receptors (D2R) have anti-inflammatory effects in the brain and kidney tissues. Mouse and human adipocytes express the (D2R); D2R protein was 10-fold greater in adipocytes from human visceral than subcutaneous tissue. However, the function of D2R in adipocytes is not well understood. The D2-like receptor agonist Quinpirole increased the protein expression of leptin and IL-6, not adiponectin and Visfatin, along with their mRNA expression (24 hr)...
February 22, 2018: Journal of Lipid Research
Glaucia Souza-Almeida, Heloisa D'Avila, Patricia E Almeida, Tatiana Luna-Gomes, Sally Liechocki, Barbara Walzog, Ingrid Hepper, Hugo Caire Castro-Faria-Neto, Patricia T Bozza, Christianne Bandeira-Melo, Clarissa M Maya-Monteiro
Leptin directly activates macrophages and lymphocytes, but the role of leptin in neutrophil activation and migration is still controversial. Here, we investigate the in vivo mechanisms of neutrophil migration induced by leptin. The intraperitoneal injection of leptin (1 mg/kg) induces a time- and concentration-dependent neutrophil influx. We did not observe the enhancement of lipid bodies/droplets in neutrophils, after leptin treatment, as we had observed previously in peritoneal macrophages. The participation of leukotriene B4 (LTB4 ) in neutrophil recruitment triggered by leptin was investigated using different strategies...
2018: Frontiers in Immunology
Jiawen Xu, Xiang Zhang, Qingqing Qian, Yiwei Wang, Hongquan Dong, Nana Li, Yanning Qian, Wenjie Jin
BACKGROUND: Astrocytes have attracted increasing attention over recent decades for their role in neuroinflammation. Histamine, a major aminergic brain neurotransmitter, has an important influence on the main activities of astrocytes, such as ion homeostasis, energy metabolism, and neurotransmitter clearance. However, little is known about the impact of histamine on astrocyte immunomodulatory function. METHODS: The expression of all known histamine receptor subtypes was examined in primary astrocytes...
February 13, 2018: Journal of Neuroinflammation
Kanako Yamamoto, Takashi Yamamoto, Masayuki Takamura, Soichiro Usui, Hisayoshi Murai, Shuichi Kaneko, Takumi Taniguchi
AIM: To evaluate the effects of mineralocorticoid receptor (MR) antagonists on mortality and inflammatory responses after hemorrhagic shock (HS) in rats. METHODS: One hundred and two male Sprague-Dawley rats were randomly assigned to one of the following three groups: Control, spironolactone (SPL), and eplerenone (EP) groups. HS was induced by the removal of blood. One half of rats were evaluated to determine mortality, hemodynamics, plasma tumor necrosis factor-alpha (TNF-α) concentrations, and arterial blood gas at 8 h after HS recovery...
February 4, 2018: World Journal of Critical Care Medicine
Biao Wang, Teng Chen, Jing Wang, Yuwei Jia, Huixun Ren, Feng Wu, Mei Hu, Yanjiong Chen
Methamphetamine (METH) elicits neuroinflammatory effects that may implicate its regulatory role on the microglial immune response. However, the mechanism underlying this remains unclear. In the present study, the effects of METH on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) productions were tested in BV-2 cells and primary microglial cells. Additionally, western blot analysis was used to examine the phosphorylation of mitogenactivated protein kinases (MAPKs)...
January 29, 2018: International Immunopharmacology
Alastair Proudfoot, Andrew Bayliffe, Cecilia M O'Kane, Tracey Wright, Adrian Serone, Philippe Jean Bareille, Vanessa Brown, Umar I Hamid, Younan Chen, Robert Wilson, Joanna Cordy, Peter Morley, Ruud de Wildt, Stuart Elborn, Matthew Hind, Edwin R Chilvers, Mark Griffiths, Charlotte Summers, Daniel Francis McAuley
BACKGROUND: Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 and TNFR2. In the setting of acute injury, selective inhibition of TNFR1 is predicted to attenuate the cell death and inflammation associated with TNF-α, while sparing or potentiating the protective effects of TNFR2 signalling. We developed a potent and selective antagonist of TNFR1 (GSK1995057) using a novel domain antibody (dAb) therapeutic and assessed its efficacy in vitro, in vivo and in a clinical trial involving healthy human subjects...
January 29, 2018: Thorax
Jay Luther, Manish Gala, Suraj J Patel, Maneesh Dave, Nynke Borren, Ramnik J Xavier, Ashwin N Ananthakrishnan
BACKGROUND: While monoclonal antibodies against tumor necrosis factor-α (TNFα) are effective in treating Crohn's disease (CD), approximately one-third of patients lose response. The mechanisms underlying this loss of response remain elusive. AIM: We sought to determine if novel biological pathways, including TNFα-independent inflammatory pathways, emerge in those with loss of response to anti-TNFα. METHODS: Using RNA microarray technology in 28 patients with CD, we examined the colonic gene expression differences between those with active inflammation in the setting of loss of response to TNFα-antagonist therapy ("loss of responders") compared to anti-TNFα naïve patients with active inflammation and those on anti-TNF therapy in disease remission...
January 25, 2018: Digestive Diseases and Sciences
Nadine Gehrke, Nadine Hövelmeyer, Ari Waisman, Beate K Straub, Julia Weinmann-Menke, Marcus A Wörns, Peter R Galle, Jörn M Schattenberg
BACKGROUND & AIMS: Interleukin (IL)-1-type cytokines including IL-1alpha, IL-1beta and interleukin-1 receptor antagonist (IL-1Ra) are among the most potent molecules of the innate immune system and exert biological activities through the ubiquitously expressed interleukin-1 receptor type 1 (IL-1RI). The role of IL-1RI in hepatocytes during acute liver failure (ALF) remains undetermined. METHODS: IL-1RI during ALF was investigated using a novel transgenic mouse model exhibiting deletion of all signaling-capable IL-1R isoforms in hepatocytes (IL-1RIHep-/-)...
January 20, 2018: Journal of Hepatology
Paula Maciel-Silva, Izabela Caldeira, Icaro de Assis Santos, Ana Claudia Oliveira Carreira, Flavia Ramos Siqueira, Eliane Antonioli, Anna Carla Goldberg, José Ernesto Belizário, Humberto Miguel Garay-Malpartida
BACKGROUND: FAM3B/PANDER is a novel cytokine-like protein that induces apoptosis in insulin-secreting beta-cells. Since in silico data revealed that FAM3B can be expressed in prostate tumors, we evaluated the putative role of this cytokine in prostate tumor progression. METHODS: FAM3B expression was analyzed by quantitative PCR in tumor tissue clinical samples and prostate tumor cell lines. Culture growth and viability of DU145 cell line were evaluated after treatment with either exogenous FAM3B protein obtained from conditioned media (CM) of 293 T cells overexpressing FAM3B or a recombinant FAM3B protein produced in a bacterial host...
January 22, 2018: BMC Cancer
Vladimir Fijačko, Marina Labor, Mirjana Fijačko, Sanda Škrinjarić-Cincar, Slavica Labor, Iva Dumbović Dubravčić, Tatjana Bačun, Aleksandar Včev, Sanja Popović-Grle, Davor Plavec
BACKGROUND: No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients. METHODS: A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium)...
January 10, 2018: Wiener Klinische Wochenschrift
Serbülent Gökhan Beyaz, Mustafa Erkan İnanmaz, Tolga Ergönenç, Onur Palabıyık, Yakup Tomak, Ayça Taş Tuna
Introduction: Inflammatory cytokines secreted from the nucleus pulposus are thought to lead to lumbar nerve root compression-like symptoms. Tumor necrosis factor-alpha (TNF-α), an inflammatory cytokine, likely plays an important role in lumbar disc hernia-related leg pain. In this experimental study, we compared the effectiveness of TNF-α antagonists administered through the intravenous or epidural route in lumbar spine pathologies. Materials and Methods: After ethics committee approval had been obtained, 24 Sprague Dawley male rats aged 70-90 days and weighing 250-300 g each were allocated to four groups...
October 2017: Anesthesia, Essays and Researches
Serena Pastore, Samuele Naviglio, Arianna Canuto, Loredana Lepore, Stefano Martelossi, Alessandro Ventura, Andrea Taddio
OBJECTIVES: Anti-tumor necrosis factor alpha (anti-TNF-α) agents are generally well tolerated, yet they can be associated with serious adverse events (SAEs) in a minority of patients. We examined the incidence of SAEs in a pediatric referral center for chronic rheumatologic and gastroenterological inflammatory disorders. METHODS: Retrospective analysis of SAEs occurring during treatment with anti-TNF-α agents in patients with juvenile idiopathic arthritis (JIA) (n = 78)  or pediatric-onset inflammatory bowel disease (IBD) (n = 105) seen at the Institute for Maternal and Child Health IRCCS "Burlo Garofolo" in Trieste, Italy, between June 2001 and February 2016...
December 6, 2017: Paediatric Drugs
Grace Xiong, Nithya Lingampalli, Jayme C B Koltsov, Lawrence L Leung, Nidhi Bhutani, William H Robinson, Constance R Chu
BACKGROUND: Autologous platelet-rich plasma (PRP) is widely used for a variety of clinical applications. However, clinical outcome studies have not consistently shown positive effects. The composition of PRP differs based on many factors. An improved understanding of factors influencing the composition of PRP is important for the optimization of PRP use. HYPOTHESIS: Age and sex influence the PRP composition in healthy patients. STUDY DESIGN: Controlled laboratory study...
February 2018: American Journal of Sports Medicine
Jingnian Song, Yanlu Ying, Wei Wang, Xianguo Liu, Xuebing Xu, Xuhong Wei, Xiangcai Ruan
The mechanisms of chronic postsurgical pain remain to be elucidated.. We reported here that skin/muscle incision and retraction (SMIR), a rat model of postsurgical pain, phosphorylated the extracellular regulated protein kinases (ERK) signaling components c-Raf, MEK (ERK kinase) and ERK1/2 in lumbar 3 dorsal root ganglion (L3 DRG) in rats. Intrathecal injection of ERK specific inhibitor SCH772984 suppressed the mechanical allodynia induced by SMIR. Further more, SMIR upregulated tumor necrosis factor alpha (TNFα) in L3 DRG, which could be inhibited by SCH772984...
November 16, 2017: Brain, Behavior, and Immunity
Ahmed F Mohamed, Mohammed F El-Yamany, Fatma A El-Batrawy, Mohamed T Abdel-Aziz
JNJ7777120, a histamine H4 receptor antagonist, was shown to be effective in different experimental settings of allergic inflammation, including contact hypersensitivity. Toll-like receptors (TLRs) are thought to function as a link between innate and adaptive immune responses to various haptens. Here, we studied the suppression of TLR signaling as a possible mechanism by which JNJ7777120 exerts its anti-inflammatory effects against the chemical hapten, fluorescein isothiocyanate (FITC). The potential anti-oxidant effect of JNJ7777120 in this model was also examined...
November 10, 2017: Inflammation
Jung-Won Hwang, Young-Tae Jeon, Young-Jin Lim, Hee-Pyoung Park
The anti-inflammatory actions of sevoflurane postconditioning are suggested as an important mechanism of sevoflurane postconditioning-induced neuroprotection against cerebral ischemia. Here, we determined whether the anti-inflammatory effects of sevoflurane postconditioning were mediated via inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway after global transient cerebral ischemia in rats. Forty-five rats were randomly assigned to five groups as follows: (1) control (10 min of ischemia, n = 10); (2) sevoflurane postconditioning (two periods of sevoflurane inhalation after ischemia for 10 min with a wash period of 10 min, n = 10); (3) resatorvid (intraperitoneal injection of a selective TLR-4 antagonist (3 mg/kg) 30 min before ischemia, n = 10); (4) sevoflurane postconditioning plus resatorvid ( n = 10), and sham ( n = 5)...
November 6, 2017: International Journal of Molecular Sciences
Melody Maarouf, Ashley K Clark, Dylan E Lee, Vivian Y Shi
PURPOSE: Targeted, immune-modulating drugs are at the forefront of therapy for HS, and a comprehensive clinical trial registry is needed to facilitate data pooling and clinical efficacy comparison. MATERIALS AND METHODS: A systematic review of the database was searched for planned, in-progress, completed, or terminated trials investigating the effect of targeted biologic therapies for hidradenitis suppurativa (HS). When results of RCTs were not available, case reports or series were included...
November 10, 2017: Journal of Dermatological Treatment
Fabian Szepanowski, Leon-Phillip Szepanowski, Anne K Mausberg, Christoph Kleinschnitz, Bernd C Kieseier, Mark Stettner
Lysophosphatidic acid (LPA) is a pleiotropic signaling lipid that acts as ligand for at least six specific G-protein coupled receptors. Schwann cells (SC) are known to mainly express the LPA1 receptor subtype. An emerging body of evidence has linked LPA with injury-induced peripheral nerve demyelination as well as neuropathic pain. However, the molecular mechanisms underlying its demyelinating effect have not been conclusively elucidated. We aimed to decipher the demyelinating effect in vitro as well as in vivo by studying markers of SC differentiation and dedifferentiation: Myelinated dorsal root ganglia (DRG) cultures were treated either with LPA, LPA plus AM095 (LPA1 antagonist) or vehicle...
October 16, 2017: Neuroscience Letters
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