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Macrophage methotrexate

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https://www.readbyqxmd.com/read/29928978/dual-functional-lipid-polymeric-hybrid-ph-responsive-nanoparticles-decorated-with-cell-penetrating-peptide-and-folate-for-therapy-against-rheumatoid-arthritis
#1
Jinlong Zhao, Xueyan Zhang, Xiangshi Sun, Menghui Zhao, Changhui Yu, Robert J Lee, Fengying Sun, Yulin Zhou, Youxin Li, Lesheng Teng
Methotrexate (MTX), as a disease modifying antirheumatic drug (DMARD), was first line drug to treat rheumatoid arthritis. However, the severe side effect during long term and high dosage usage limit its application. The aim of this study was to develop dual-functional lipid polymeric hybrid pH-responsive nanoparticles to deliver MTX to inflamed joints selectively. The designed MTX loaded stearic acid-octa-arginine and folic acid decorated poly lactic-co-glycolic acid (PLGA) -PK3-based lipid polymeric hybrid nanoparticles (Sta-R8-FA-PPLPNs/MTX) were composed of PK3, Folate-PEG-PLGA, egg PC, and Sta-R8...
June 18, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29920284/an-in-vitro-test-system-for-compounds-that-modulate-human-inflammatory-macrophage-polarization
#2
Hiromi Shiratori, Carmen Feinweber, Sonja Luckhardt, Nadja Wallner, Gerd Geisslinger, Andreas Weigert, Michael J Parnham
Macrophages undergo activation by pathophysiological stimuli to pro-inflammatory and bactericidal, or wound-healing and anti-inflammatory phenotypes, termed M1 or M2, respectively. Dysregulation of the M1-M2 balance is often associated with inflammatory diseases. Therefore, mechanisms of macrophage polarization may reveal new drug targets. We profiled six compounds with claimed modulatory effects on macrophage polarization using peripheral blood monocyte-derived macrophages. Based on the distinct mRNA or protein expression in macrophages stimulated either with M1 [lipopolysaccharide (LPS) + interferon-γ, IFNγ] or M2 interleukin-4 (IL-4) stimuli, we selected a combination of M1 (IL1β, tumor necrosis factor-α,TNFα, CC chemokine receptor 7, CCR7 and CD80) and M2 (chemokine (C-C motif) ligand 22, CCL22, CD200R and mannose receptor C type 1, MRC1) markers to monitor drug effects on "M1 polarization" or cells "pre-polarized to M1"...
June 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29862296/a-synbiotic-with-tumor-necrosis-factor-%C3%AE-inhibitory-activity-ameliorates-experimental-jejunoileal-mucosal-injury
#3
Ryoki Takahashi, Takayasu Noguchi, Yoko Mizoguchi, Tadashi Shimoyama, Teruko Nakazawa, Tohru Ikuta
Despite the recent development of biological modifiers for inflammatory bowel diseases (IBD), there continues to be considerable interest in fermented medicines because of its negligible adverse effects. We previously showed that the synbiotic Gut Working Tablet (GWT) alleviates experimental colitis. Here we show that GWT is capable of ameliorating jejunoileal mucosal injury, which is frequently seen with IBD. We created experimental jejunoileal mucositis in rats by injection of methotrexate (MTX) which increases intestinal permeability, a hallmark finding of IBD...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29808814/-affected-liver-biochemistry-in-children-with-rheumatic-diseases
#4
Helene Mygind Wolsk, Marianne Hørby Jørgensen, Susan Nielsen
Children with rheumatic diseases often have elevated liver biochemistry. This can be triggered by medical treatment, e.g. methotrexate can induce liver injury ranging from mild to severe. Autoimmune hepatitis and sclerosing cholangitis are also seen in conjunction with rheumatic diseases, and early diagnosis and treatment is crucial to prevent development of cirrhosis and liver transplantation. Macrophage activation syndrome is a rare but important differential diagnosis as it is a potentially fatal complication to systemic rheumatic diseases, causing liver dysfunction and multi-organ failure...
May 28, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29802817/prophylactic-and-therapeutic-activity-of-alkaline-phosphatase-in-arthritic-rats-single-agent-effects-of-alkaline-phosphatase-and-synergistic-effects-in-combination-with-methotrexate
#5
Durga M S H Chandrupatla, Carla F M Molthoff, Wayne I G R Ritsema, Ricardo Vos, Eline Elshof, Takami Matsuyama, Philip S Low, René J P Musters, Anthony Hammond, Albert D Windhorst, Adriaan A Lammertsma, Conny J van der Laken, Ruud Brands, Gerrit Jansen
Alkaline phosphatase (AP) is a gate-keeper of innate immune system responses by detoxifying inflammation triggering moieties released from endogenous and external sources. We examined whether AP's broad mechanism of action constitutes a safe therapeutic, either as single agent or combined with methotrexate (MTX), for chronic inflammatory disorders, for example, rheumatoid arthritis (RA). A rat model for RA was used with repeated intra-articular methylated bovine serum albumin (mBSA) injections in 1 knee ("arthritic" knee), with the contralateral knee serving as internal control...
May 17, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29780382/extracellular-purine-metabolism-is-the-switchboard-of-immunosuppressive-macrophages-and-a-novel-target-to-treat-diseases-with-macrophage-imbalances
#6
Anna Ohradanova-Repic, Christian Machacek, Celine Charvet, Franck Lager, Delphine Le Roux, René Platzer, Vladimir Leksa, Goran Mitulovic, Thomas R Burkard, Gerhard J Zlabinger, Michael B Fischer, Vincent Feuillet, Gilles Renault, Stephan Blüml, Miroslav Benko, Miloslav Suchanek, Johannes B Huppa, Takami Matsuyama, Artur Cavaco-Paulo, Georges Bismuth, Hannes Stockinger
If misregulated, macrophage (Mϕ)-T cell interactions can drive chronic inflammation thereby causing diseases, such as rheumatoid arthritis (RA). We report that in a proinflammatory environment, granulocyte-Mϕ (GM-CSF)- and Mϕ colony-stimulating factor (M-CSF)-dependent Mϕs have dichotomous effects on T cell activity. While GM-CSF-dependent Mϕs show a highly stimulatory activity typical for M1 Mϕs, M-CSF-dependent Mϕs, marked by folate receptor β (FRβ), adopt an immunosuppressive M2 phenotype. We find the latter to be caused by the purinergic pathway that directs release of extracellular ATP and its conversion to immunosuppressive adenosine by co-expressed CD39 and CD73...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779420/regression-of-atherosclerotic-plaques-of-cholesterol-fed-rabbits-by-combined-chemotherapy-with-paclitaxel-and-methotrexate-carried-in-lipid-core-nanoparticles
#7
Fernando L T Gomes, Raul C Maranhão, Elaine R Tavares, Priscila O Carvalho, Maria L Higuchi, Fernando R Mattos, Fabio G Pitta, Sergio A Hatab, Roberto Kalil-Filho, Carlos V Serrano
In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29738359/genomic-profile-and-pathologic-features-of-diffuse-large-b-cell-lymphoma-subtype-of-methotrexate-associated-lymphoproliferative-disorder-in-rheumatoid-arthritis-patients
#8
Joaquim Carreras, Yara Yukie Kikuti, Masashi Miyaoka, Shinichiro Hiraiwa, Sakura Tomita, Haruka Ikoma, Yusuke Kondo, Sawako Shiraiwa, Kiyoshi Ando, Shinji Sato, Yasuo Suzuki, Ikuo Miura, Giovanna Roncador, Naoya Nakamura
Rheumatoid arthritis patients often develop the diffuse large B-cell lymphoma subtype of methotrexate-associated lymphoproliferative disorder (DLBCL). We characterized the genomic profile and pathologic characteristics of 20 biopsies using an integrative approach. DLBCL was associated with extranodal involvement, a high/high-intermediate international prognostic index in 53% of cases, and responded to MTX withdrawal. The phenotype was nongerminal center B-cell in 85% of samples and Epstein-Barr encoding region positive (EBER) in 65%, with a high proliferation index and intermediate MYC expression levels...
July 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29708588/anti-arthritic-properties-of-crude-extract-from-chenopodium-ambrosioides-l-leaves
#9
Wanderson S Pereira, Girlaine P da Silva, Mariana V Vigliano, Nathalia R F Leal, Fabiana A Pinto, Daniele C Fernandes, Shirley V M Santos, Thiago Martino, Johnny R Nascimento, Ana Paula S de Azevedo, Eduardo N Fonseca, Leosvaldo S M Velozo, Lauro R Souza Neto, Frederico F Bastos, Elyzabeth A Portari, Kátia C Carvalho Sabino, Flávia Nascimento, Marsen G P Coelho
OBJECTIVES: To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. METHODS: Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology...
April 30, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29681783/imaging-and-methotrexate-response-monitoring-of-systemic-inflammation-in-arthritic-rats-employing-the-macrophage-pet-tracer-18-f-fluoro-peg-folate
#10
Durga M S H Chandrupatla, Gerrit Jansen, Elise Mantel, Philip S Low, Takami Matsuyama, René P Musters, Albert D Windhorst, Adriaan A Lammertsma, Carla F M Molthoff, Conny J van der Laken
Background: In rheumatoid arthritis, articular inflammation is a hallmark of disease, while the involvement of extra-articular tissues is less well defined. Here, we examined the feasibility of PET imaging with the macrophage tracer [18 F]fluoro-PEG-folate, targeting folate receptor β (FR β ), to monitor systemic inflammatory disease in liver and spleen of arthritic rats before and after methotrexate (MTX) treatment. Methods: [18 F]Fluoro-PEG-folate PET scans (60 min) were acquired in saline- and MTX-treated (1 mg/kg, 4x) arthritic rats, followed by tissue resection and radiotracer distribution analysis...
2018: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29546609/igg4-related-disease-beyond-glucocorticoids
#11
REVIEW
Mitsuhiro Akiyama, Tsutomu Takeuchi
IgG4-related disease is a heterogeneous immune-mediated fibroinflammatory condition that can affect every single organ. This disease is more prevalent in the elderly (the mean age of patients is above 60 years) and the prevalence rate is estimated to be over 4.6 per 100,000 population. Before making a diagnosis, the exclusion of malignancies, lymphoma, anti-neutrophil cytoplasmic antibody-associated vasculitis, multicentric Castleman disease, and other mimickers is crucial for appropriate treatment. Broad management guidelines have been published emphasizing the need for prompt treatment and the use of glucocorticoids as first-line drug therapy for induction of remission...
April 2018: Drugs & Aging
https://www.readbyqxmd.com/read/29542334/bayesian-comparative-effectiveness-study-of-four-consensus-treatment-plans-for-initial-management-of-systemic-juvenile-idiopathic-arthritis-first-line-options-for-systemic-juvenile-idiopathic-arthritis-treatment-frost
#12
Peter A Nigrovic, Timothy Beukelman, George Tomlinson, Brian M Feldman, Laura E Schanberg, Yukiko Kimura
BACKGROUND: Systemic juvenile idiopathic arthritis is a rare febrile arthritis of childhood characterized by a potentially severe course, including prolonged glucocorticoid exposure, growth failure, destructive arthritis, and life-threatening macrophage activation syndrome. Early cytokine-blocking biologic therapy may improve long-term outcomes, although some systemic juvenile idiopathic arthritis patients respond well to non-biologic treatment, leaving optimal management undefined. Consequently, treatment of new-onset systemic juvenile idiopathic arthritis by expert clinicians varies widely...
March 1, 2018: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/29490676/pharmacological-characterisation-of-cr6086-a-potent-prostaglandin-e-2-receptor-4-antagonist-as-a-new-potential-disease-modifying-anti-rheumatic-drug
#13
Gianfranco Caselli, Albino Bonazzi, Marco Lanza, Flora Ferrari, Daniele Maggioni, Cristian Ferioli, Roberto Giambelli, Eleonora Comi, Silvia Zerbi, Marco Perrella, Ornella Letari, Elena Di Luccio, Milena Colovic, Stefano Persiani, Tiziano Zanelli, Laura Mennuni, Tiziana Piepoli, Lucio Claudio Rovati
BACKGROUND: Prostaglandin E2 (PGE2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively...
March 1, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29431121/methotrexate-limits-inflammation-through-an-a20-dependent-cross-tolerance-mechanism
#14
Cristina Municio, Ángeles Dominguez-Soto, Sara Fuentelsaz-Romero, Amalia Lamana, Nuria Montes, Víctor D Cuevas, Raquel García Campos, José L Pablos, Isidoro González-Álvaro, Amaya Puig-Kröger
OBJECTIVES: Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but the mechanism of its anti-inflammatory action is not fully understood. In RA, macrophages display a proinflammatory polarisation profile that resembles granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages and the response to MTX is only observed in thymidylate synthase+ GM-CSF-dependent macrophages. To determine the molecular basis for the MTX anti-inflammatory action, we explored toll-like receptor (TLR), RA synovial fluid (RASF) and tumour necrosis factor receptor (TNFR)-initiated signalling in MTX-exposed GM-CSF-primed macrophages...
May 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29407968/aryl-thiosemicarbazones-for-the-treatment-of-trypanosomatidic-infections
#15
Pasquale Linciano, Carolina B Moraes, Laura M Alcantara, Caio H Franco, Bruno Pascoalino, Lucio H Freitas-Junior, Sara Macedo, Nuno Santarem, Anabela Cordeiro-da-Silva, Sheraz Gul, Gesa Witt, Maria Kuzikov, Bernhard Ellinger, Stefania Ferrari, Rosaria Luciani, Antonio Quotadamo, Luca Costantino, Maria Paola Costi
Basing on a library of thiadiazole derivatives showing anti-trypanosomatidic activity, we have considered the thiadiazoles opened forms and reaction intermediates, thiosemicarbazones, as compounds of interest for phenotypic screening against Trypanosoma brucei (Tb), intracellular amastigote form of Leishmania infantum (Li) and Trypanosoma cruzi (Tc). Similar compounds have already shown interesting activity against the same organisms. The compounds were particularly effective against T. brucei and T. cruzi...
February 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29361199/mavrilimumab-a-fully-human-granulocyte-macrophage-colony-stimulating-factor-receptor-%C3%AE-monoclonal-antibody-long-term-safety-and-efficacy-in-patients-with-rheumatoid-arthritis
#16
Gerd R Burmester, Iain B McInnes, Joel M Kremer, Pedro Miranda, Jiří Vencovský, Alex Godwood, Marius Albulescu, M Alex Michaels, Xiang Guo, David Close, Michael Weinblatt
OBJECTIVE: Mavrilimumab, a human monoclonal antibody, targets granulocyte-macrophage colony-stimulating factor receptor α. We undertook to determine the long-term safety and efficacy of mavrilimumab in rheumatoid arthritis patients in 2 phase IIb studies (1071 and 1107) and in 1 open-label extension study (ClinicalTrials.gov identifier: NCT01712399). METHODS: In study 1071, patients with an inadequate response to disease-modifying antirheumatic drugs (DMARDs) received mavrilimumab (30, 100, or 150 mg) or placebo every other week plus methotrexate...
May 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29273180/-multiple-facets-of-ada2-deficiency-vasculitis-auto-inflammatory-disease-and-immunodeficiency-a-literature-review-of-135-cases-from-literature
#17
A Fayand, G Sarrabay, A Belot, V Hentgen, I Kone-Paut, G Grateau, I Melki, S Georgin-Lavialle
Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations...
April 2018: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29228558/1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol-ameliorates-arthritic-joints-through-reducing-neutrophil-infiltration-mediated-by-il-6-stat3-and-mip-2-activation
#18
Young-Jun Kim, Jae Min Shin, Su-Hyun Shin, Joo Heon Kim, Ki-Young Sohn, Heung-Jae Kim, Jong-Koo Kang, Sun Young Yoon, Jae Wha Kim
The pathogenesis of rheumatoid arthritis (RA) has been implicated neutrophil extracellular traps (NETs) formation which could generate autoantigen. Neutrophil contributes to initiate and maintain the inflammatory process in the joint. In this study, we show that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) decreases neutrophil migration by regulating the activity of STAT3, a regulator of IL-6 and MIP-2 expression. PLAG caused a decrease in IL-6 production in the RAW264.7 macrophage cell line and in rheumatoid arthritis-fibroblast-like synoviocytes via the regulation of STAT3 signaling without affecting NF-κB signaling...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29166574/altered-tnf-%C3%AE-response-by-aconibal%C3%A2-and-methotrexate-in-a-lipopolysaccharide-induced-setting-of-inflammatory-conditions-potential-on-a-synergistic-combination
#19
Gunhyuk Park, Seung Hoon Lee, Ji-Ye Han, Dal-Seok Oh
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii (AC) is a common herbal medicine used as anti-inflammatory and analgesic agent in Eastern Asia. In Korea, a commercial processed AC (Aconibal®) is traditionally used to treat the symptoms of spondylosis deformans and rheumatic pain. AIM OF STUDY: Rheumatoid arthritis (RA) is systemic and autoimmune disease characterized by chronic inflammation. Methotrexate (MTX) is often the first-line therapy for RA. If MTX monotherapy is ineffective or RA is initially severe, adding a tumor necrosis factor alpha (TNF-α) inhibitor to the treatment can be beneficial...
March 1, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29154446/transmission-electron-microscopy-helpfulness-in-whipple-s-disease-masked-by-immunosuppressant-therapy-for-arthritis
#20
Alessandra Loiodice, Giuseppe Losurdo, Andrea Iannone, Roberta Rossi, Maria Grazia Fiore, Domenico Piscitelli
A 61-year-old woman received a diagnosis of undifferentiated non-erosive arthritis in 2010 and assumed methotrexate and steroids in 2014. After 1 year, she experienced watery diarrhea, vomiting, fever, weight loss, and severe hypoalbuminemia, thus being admitted into our Unit. Esophagogastroduodenoscopy showed duodenal lymphangiectasia and duodenal biopsy samples several foamy PAS-positive macrophages and villous subtotal atrophy. Transmission electron microscope demonstrated several extracellular and intracellular rod-shaped bacteria (Tropheryma whipplei)...
January 2018: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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