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Th17 methotrexate

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https://www.readbyqxmd.com/read/29599672/the-effect-of-subcutaneous-methotrexate-on-markers-of-metabolic-syndrome-in-psoriatic-patients-preliminary-report
#1
Agnieszka Owczarczyk-Saczonek, Marek Drozdowski, Agata Maciejewska-Radomska, Dariusz Choszcz, Waldemar Placek
Introduction: Methotrexate (MTX) has anti-proliferative and anti-inflammatory effects in psoriasis. Moreover, low doses can reduce the risk of developing cardiovascular diseases. It turns out that psoriasis and atherosclerosis have a similar pathogenetic mechanism: the same pro-inflammatory cytokines, Th1 and Th17, are involved in both diseases. Aim: To evaluate the effects of metabolic markers, protective cytokines (interleukin 10 (IL-10), transforming growth factor β (TGF-β)) and a marker of endothelial damage (endocan) in patients with plaque psoriasis...
February 2018: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/29510190/satb1-defines-a-subtype-of-cutaneous-cd30-lymphoproliferative-disorders-associated-with-a-t-helper-17-cytokine-profile
#2
Jingru Sun, Shengguo Yi, Lei Qiu, Wenjing Fu, Anqi Wang, Fengjie Liu, Lin Wang, Tingting Wang, Hao Chen, Lei Wang, Marshall E Kadin, Ping Tu, Yang Wang
Cutaneous CD30+ lymphoproliferative disorder (CD30+LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (PCALCL), comprises the second most common group of cutaneous T cell lymphoma. Previously, we reported that special AT-rich sequence-binding protein1 (SATB1), a thymocyte specific chromatin organizer, was over-expressed and promoted malignant T-cell proliferation in a portion of CD30+LPDs. Here, we investigated the expression pattern of SATB1 in CD30+LPDs with a large cohort of patient samples, and examined the potential of SATB1 as a molecular marker to classify CD30+LPDs with differential clinicopathological behaviors...
March 3, 2018: Journal of Investigative Dermatology
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
#3
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/29410374/a-novel-combination-of-astilbin-and-low-dose-methotrexate-respectively-targeting-a-2a-ar-and-its-ligand-adenosine-for-the-treatment-of-collagen-induced-arthritis
#4
Yuxiang Ma, Zhe Gao, Fang Xu, Li Liu, Qiong Luo, Yan Shen, Xuefeng Wu, Xingxin Wu, Yang Sun, Xudong Wu, Qiang Xu
Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) treatment with frequently serious adverse effects. Therefore, combination of low-dose MTX with other drugs is often used in clinic. In this study, we investigated the improvement of astilbin and low-dose MTX combination on collagen-induced arthritis in DBA/1J mice. Results showed that the clinic score, incidence rate, paw swelling, pathological changes of joints and rheumatoid factors were more alleviated in combination therapy than MTX or astilbin alone group...
February 2, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29222448/effect-of-qianghuo-erhuang-decoction-on-t-regulatory-and-t-helper-17-cells-in-treatment-of-adjuvant-induced-arthritis-in-rats
#5
Can Qian, Mei Kuang, Yong Wang
QianghuoErhuang Decoction (QED) is an effective recipe in treating rheumatoid arthritis. The present study aimed to explore the effects of QED on Treg and Th17 in adjuvant arthritis (AA) model. The study included 6 group rats: normal control group, AA group, AA + methotrexate (MTX) group, AA + high, moderate, and low dose QED groups. The arthritis score was significantly decreased in the MTX and high-dose QED groups compared with the AA group on days 24 and 28 (P < 0.01), respectively. The synovial tissue inflammation was attenuated by histological observation, and the proliferation of splenocytes was significantly inhibited in MTX and high-dose QED groups (P < 0...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29034454/successful-treatment-of-sapho-syndrome-with-apremilast
#6
S Adamo, J Nilsson, A Krebs, U Steiner, A Cozzio, L E French, A G A Kolios
SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a rare disease with inflammatory osteoarticular and skin involvement. The pathogenesis of SAPHO syndrome remains unclear, but evidence suggests it may be an autoinflammatory disease triggered upon exposure to infectious agents in genetically predisposed individuals. Induction of the interleukin (IL)-23/T helper 17 axis in addition to neutrophil activation seem to play a key role, and therapies targeting these immunological pathways, including tumour necrosis factor (TNF) inhibitors, ustekinumab, secukinumab and the IL-1 inhibitor anakinra, are potential treatment options that need further investigation...
October 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28736556/ras-signaling-inhibitors-attenuate-disease-in-adjuvant-induced-arthritis-via-targeting-pathogenic-antigen-specific-th17-type-cells
#7
Morad Zayoud, Victoria Marcu-Malina, Einav Vax, Jasmine Jacob-Hirsch, Galit Elad-Sfadia, Iris Barshack, Yoel Kloog, Itamar Goldstein
The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#8
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Taniai-Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signalling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
January 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/28329473/successful-treatment-of-recalcitrant-discoid-lupus-erythematosus-with-ustekinumab
#9
Alberto Romero-Maté, Carmen García-Donoso, Almudena Hernández-Núñez, Cristina Martínez-Morán, Amalia Moreno-Torres, Jesús Borbujo-Martínez
We report a 52-year old woman with a 28-year historyof disfiguring facial discoid lupus erythematosus(DLE), persistent despite both classical therapiesand rituximab. Ustekinumab 45 mg was started incombination with methotrexate and intralesionalcorticosteroids. Methotrexate and intralesionalcorticosteroids were withdrawn 30 months later andustekinumab maintained as monotherapy. Fortyeight months later stable improvement was achievedwithout side effects. Only nine patients with cutaneouslupus erythematosus (CLE) treated with ustekinumabhave been reported to date...
January 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28117352/il-22-producing-cd4-t-cells-in-the-treatment-response-of-rheumatoid-arthritis-to-combination-therapy-with-methotrexate-and-leflunomide
#10
Wei Zhong, Ling Zhao, Tao Liu, Zhenyu Jiang
T cells are key players in immune-mediated rheumatoid arthritis (RA). We previously reported that interleukin (IL)-22(+)CD4(+)T helper (IL-22(+) Th) cells and IL-22 critically control the pathogenesis of RA. Here we monitored circulating levels of different IL-22(+) Th cell subsets and measured plasma levels of IL-22, IL-17, and interferon (IFN)-γ in 60 patients with active RA following 12-week combination methotrexate (MTX) and leflunomide (LEF) therapy (MTX+LEF) and 20 healthy individuals. We found the frequencies of circulating IFN-γ(-)IL-17(-)IL-22(+) (Th22), IFN-γ(-)IL-17(+) (total Th17), IFN-γ(+)IL-17(-)IL-22(+) (IL-22(+)Th1) cells, and IFN-γ(-)IL-17(+)IL-22(+) (IL-22(+)Th17) cells, as well as the plasma levels of IL-22, IL-17 and IFN-γ to be significantly reduced in RA patients that responded to treatment, but not in non-responders...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27733943/updates-in-anca-associated-vasculitis
#11
REVIEW
Christian Pagnoux
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated...
September 2016: European Journal of Rheumatology
https://www.readbyqxmd.com/read/27322646/interleukin-6-il-6-receptor-antagonist-protects-against-rheumatoid-arthritis
#12
Songsong Li, Zhenzhou Wu, Ling Li, Xuehua Liu
BACKGROUND The aim of this study was to investigate the protective effect of interleukin-6 (IL-6) receptor antagonist tocilizumab (TCZ) on rheumatoid arthritis (RA) and its related mechanism. MATERIAL AND METHODS Thirty RA patients receiving long-term methotrexate therapy at moderate and severe active stages were selected and treated with TCZ 8 mg/kg/time iv gtt intravenously guttae every 4 weeks. Peripheral blood was extracted before and 24 weeks after TCZ treatment. Peripheral blood mononuclear cells (PBMC) were collected by density gradient centrifugation...
June 20, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27240060/pathophysiological-basis-of-systemic-treatments-in-psoriasis
#13
Sebastian Volc, Kamran Ghoreschi
Over the past 15 years, the spectrum of systemic antipsoriatic treatments has dramatically expanded. Until the end of the last millennium, systemic therapy had been restricted to four oral agents: methotrexate, cyclosporine, acitretin, and fumaric acid esters. Today, there are additionally seven biologics and one new oral antipsoriatic drug, as well as the first available biosimilars. Six more biologics with novel target structures and at least four biosimilars are currently being developed (phase III). This progress has been based on new insights into the pathogenesis of psoriasis, in which tumor necrosis factor and especially Th17 immune responses with their associated cytokines interleukin 23 and 17 play a key role...
June 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/27123445/elevated-ratio-of-th17-cell-derived-th1-cells-cd161-th1-cells-to-cd161-th17-cells-in-peripheral-blood-of-early-onset-rheumatoid-arthritis-patients
#14
Shigeru Kotake, Yuki Nanke, Toru Yago, Manabu Kawamoto, Tsuyoshi Kobashigawa, Hisashi Yamanaka
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27025861/the-inflammatory-response-in-psoriasis-a-comprehensive-review
#15
REVIEW
Yaxiong Deng, Christopher Chang, Qianjin Lu
Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. However, psoriasis is thought to result from a combination of genetic, epigenetic, and environmental influences. Recent studies have identified that epigenetic factors including dysregulated DNA methylation levels, abnormal histone modification and microRNAs expressions are involved in the development of psoriasis...
June 2016: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/26268060/-1-25-oh-2-vitamin-d3-attenuates-th17-related-cytokines-expression-in-peripheral-blood-mononuclear-cells-in-patients-with-early-diagnosed-rheumatoid-arthritis
#16
Hongyan Wen, Jing Luo, Xiaoying Zhang, Chen Zhang, Xiangcong Zhao, Xin Wang, Xiaofeng Li
OBJECTIVE: To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] on T helper cell type 17 (Th17) cytokines and therapeutic mechanism in patients with rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected. The PBMCs were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the absence or presence of 1,25(OH)₂D₃and methotrexate (MTX). After co-culture, the serum levels of Th17 cytokines interleukin (IL)-17, IL-6, tumour necrosis factor alpha (TNFα) were analyzed by cytometric bead array (CBA)...
April 2015: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/26221616/dc-based-immunotherapy-combined-with-low-dose-methotrexate-effective-in-the-treatment-of-advanced-cia-in-mice
#17
Jun-Eui Park, Jinah Jang, Ji-Hye Choi, Mi-Sun Kang, Yun-Ju Woo, Young-Rim Seong, Chan-Bum Choi, Hye-Soon Lee, Sang-Cheol Bae, Yong-Soo Bae
We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs...
2015: Journal of Immunology Research
https://www.readbyqxmd.com/read/26152731/recent-progress-and-perspective-in-jak-inhibitors-for-rheumatoid-arthritis-from-bench-to-bedside
#18
REVIEW
Yoshiya Tanaka
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation and joint destruction. However, the combined use of synthetic disease-modifying anti-rheumatic drug (DMARD) such as methotrexate and a biological DMARD targeting tumour necrosis factor (TNF) has revolutionized treatment of RA. Clinical remission is a realistic target to treat and the maintenance of remission has produced significant improvements in structural and function outcomes. However, biological DMARDs are limited to intravenous or subcutaneous uses and orally available small but strong products have been developed...
September 2015: Journal of Biochemistry
https://www.readbyqxmd.com/read/26087385/effects-of-transplantation-of-ctla4ig-overexpressing-adipose-tissue-derived-mesenchymal-stem-cells-in-mice-with-sustained-severe-rheumatoid-arthritis
#19
Eun Wha Choi, Il Seob Shin, Ji Woo Song, MinJae Lee, Tae Won Yun, Jehoon Yang, Kyu-Sil Choi, Sung-Joo Kim
CTLA4Ig has therapeutic potential for rheumatoid arthritis patients unresponsive to methotrexate (MTX) or TNF-α blockers. However, recombinant CTLA4Ig proteins are short acting and expensive. Adipose tissue-derived mesenchymal stem cells (ASCs) present an ideal stem cell source for practical regenerative medicine due to their abundant availability and their beneficial properties including immunomodulation, homing activity, paracrine effects, and differentiation ability. Therefore, we aimed to determine whether CTLA4Ig and human ASCs show synergistic effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in a mouse model...
2016: Cell Transplantation
https://www.readbyqxmd.com/read/25946554/ccl20-and-il22-messenger-rna-expression-after-adalimumab-vs-methotrexate-treatment-of-psoriasis-a-randomized-clinical-trial
#20
RANDOMIZED CONTROLLED TRIAL
Ari M Goldminz, Mayte Suárez-Fariñas, Andrew C Wang, Nicole Dumont, James G Krueger, Alice B Gottlieb
IMPORTANCE: Methotrexate is a first-line systemic agent for treating of psoriasis, although its onset of effects is slower and overall it is less effective than tumor necrosis factor blockers. OBJECTIVE: To differentiate the response of psoriatic disease to adalimumab and methotrexate sodium. DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized, assessor-blind, 2-arm clinical trial of 30 patients from the outpatient dermatology center of Tufts Medical Center, enrolled from August 18, 2009, to October 11, 2011...
August 2015: JAMA Dermatology
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