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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/28933132/effects-of-secukinumab-on-serum-adipocytokines-preliminary-data
#1
A Fassio, D Gatti, P Gisondi, G Girolomoni, O Viapiana, A Giollo, M Zamboni, M Rossini, L Idolazzi
Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects joints, connective tissues and the axial skeleton. Metabolic syndrome is an independent risk factor for psoriasis (Pso) development and is associated with more severe forms of Pso. Adipocytokines are secreted by white adipose tissue and are thought to link obesity with the development of metabolic and cardiovascular diseases. Secukinumab is a new monoclonal antibody with a different mechanism of action. This antibody selectively binds to and neutralizes interleukin-17 (IL-17) and it has shown efficacy in the treatment of PsA...
September 21, 2017: Reumatismo
https://www.readbyqxmd.com/read/28911642/lactobacillus-pentosus-gmnl-77-inhibits-skin-lesions-in%C3%A2-imiquimod-induced-psoriasis-like-mice
#2
Yi-Hsing Chen, Chieh-Shan Wu, Ya-Husan Chao, Chi-Chen Lin, Hui-Yun Tsai, Yi-Rong Li, Yi-Zhen Chen, Wan-Hua Tsai, Yu-Kuo Chen
Psoriasis, which is regarded as a T-cell-mediated chronic inflammatory skin disease, is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. In this study, we aimed to determine the in vivo effect of a potentially probiotic strain, Lactobacillus pentosus GMNL-77, in imiquimod-induced epidermal hyperplasia and psoriasis-like skin inflammation in BALB/c mice. Oral administration of L. pentosus GMNL-77 significantly decreased erythematous scaling lesions. Real-time polymerase chain reaction showed that treatment with L...
July 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904916/prevalence-of-metabolic-syndrome-in-psoriasis-and-levels-of-interleukin-6-and-tumor-necrosis-factor-%C3%AE-in-psoriasis-patients-with-metabolic-syndrome-indian-tertiary-care-hospital-study
#3
Surjit Singh, Sunil Dogra, Nusrat Shafiq, Anil Bhansali, Samir Malhotra
BACKGROUND: Psoriasis is a chronic inflammatory multisystem disease, found to be associated with metabolic syndrome (MS) and increased levels of cytokines. To evaluate the prevalence of MS in psoriasis and to determine the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in psoriasis patients with MS. METHODS: Observational study on 334 psoriasis patients and 230 controls. MS was diagnosed by the presence of three or more criteria of original, revised, and modified National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III)...
July 2017: International Journal of Applied and Basic Medical Research
https://www.readbyqxmd.com/read/28903122/impact-of-ixekizumab-treatment-on-depressive-symptoms-and-systemic-inflammation-in-patients-with-moderate-to-severe-psoriasis-an-integrated-analysis-of-three-phase-3-clinical-studies
#4
Christopher E M Griffiths, Maurizio Fava, Andrew H Miller, James Russell, Susan G Ball, Wen Xu, Nayan Acharya, Mark Hyman Rapaport
BACKGROUND: Depression is a common comorbidity in psoriasis, and both conditions are associated with systemic inflammation. The efficacy of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, was evaluated in patients with moderate-to-severe plaque psoriasis (psoriasis) and depressive symptoms that were at least moderately severe. METHODS: Data were integrated from 3 randomized, double-blind, controlled phase 3 trials. At baseline and week 12, depressive symptoms and inflammation were assessed by the 16-item Quick Inventory of Depressive Symptomology - Self-Report (QIDS-SR16) and by a high-sensitivity assay of serum C-reactive protein (hsCRP), respectively...
September 14, 2017: Psychotherapy and Psychosomatics
https://www.readbyqxmd.com/read/28899951/lowering-interleukin-12-activity-improves-myocardial-and-vascular-function-compared-with-tumor-necrosis-factor-a-antagonism-or-cyclosporine-in-psoriasis
#5
Ignatios Ikonomidis, Evangelia Papadavid, George Makavos, Ioanna Andreadou, Maria Varoudi, Kostas Gravanis, Kostas Theodoropoulos, George Pavlidis, Helen Triantafyllidi, Paraskevi Moutsatsou, Christina Panagiotou, John Parissis, Efstathios Iliodromitis, John Lekakis, Dimitrios Rigopoulos
BACKGROUND: Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis. METHODS AND RESULTS: One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a...
September 2017: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28895664/the-severe-and-acute-complications-of-the-biologics-in-psoriasis
#6
Elias Oussedik, Nupur U Patel, Devin R Cash, Angela S Gupta, Steven R Feldman
Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold-standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha (TNF-alpha) inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 inhibitors (secukinumab and ixekizumab)...
September 12, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28894050/compounds-of-psoriasis-with-obesity-and-overweight
#7
Agnieszka Owczarczyk-Saczonek, Waldemar Placek
Many epidemiological studies have confirmed the relationship of obesity and psoriasis, and it is believed that obesity is an independent risk factor for its development and is associated with a worse prognosis. Furthermore, the reduction of body weight, using low-calorie diet combined with exercise, reduces the severity of psoriasis.Visceral adipose tissue is the largest endocrine organ, producing proinflammatory cytokines (TNF-α, IL-6, IL-17) and adipokines (adiponectin, omentin, chemerin). They participate in the development of dyslipidemia, insulin resistance, diabetes, and consequently of the cardiovascular diseases...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28890293/epidermal-barrier-reaction-to-an-in-vitro-psoriatic-microenvironment
#8
Elena Donetti, Laura Cornaghi, Francesca Arnaboldi, Federica Ricceri, Leonardo Pescitelli, Martina Maiocchi, Francesco Carriero, Franz Baruffaldi Preis, Francesca Prignano
Keratinocytes (KCs) and Langerhans cells (LCs) contribute to create the epidermal barrier. To form a functional epidermis, KCs express filaggrin and Toll-like Receptors (TLRs). LCs are the first line of epidermal defence and can be activated by interleukin (IL)-17 and Tumor Necrosis Factor (TNF)-alpha. In psoriasis, an alteration of TLR expression, a defective expression of filaggrin, and LC activation occur. In organotypic cultures of human skin we investigated the interplay between IL-17 and TNF-alpha on i) expression of filaggrin, TLR2, 7 and 9, and Nuclear Factor (NF)-kB localization by immunofluorescence and ii) LC ultrastructural features by transmission electron microscopy...
September 7, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28887948/psoriasis-pathogenesis-and-the-development-of-novel-targeted-immune-therapies
#9
REVIEW
Jason E Hawkes, Tom C Chan, James G Krueger
Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, autoantigens, and multiple environmental factors. Over the last 2 decades, research has unequivocally shown that psoriasis represents a bona fide T cell-mediated disease primarily driven by pathogenic T cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/type 17 T-cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition...
September 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28887107/efficacy-of-systemic-treatments-of-psoriasis-on-pruritus-a-systemic-literature-review-and-meta-analysis
#10
Chloé Théréné, Emilie Brenaut, Thomas Barnetche, Laurent Misery
In the course of the last 30 years, several studies have clearly documented that pruritus is a very frequent symptom of psoriasis and its impact on the patients' quality of life. The variety of available systemic treatments for psoriasis is increasing rapidly. Our objective was to assess their efficacy on pruritus based on a systematic literature review. A systematic literature search was performed using PubMed and Trip Database (from January 1990 to September 2016) to find published clinical trials for the treatments of psoriasis, then a meta-analysis was performed...
September 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28881648/correlation-between-microrna-143-in-peripheral-blood-mononuclear-cells-and-disease-severity-in-patients-with-psoriasis-vulgaris
#11
Yi-Zhi Zheng, Chun-Feng Chen, Li-Ying Jia, Tu-Gen Yu, Jie Sun, Xiao-Yong Wang
This study aims to explore the correlation between microRNA-143 (miR-143) expression in peripheral blood mononuclear cells (PBMCs) and disease severity in patients with psoriasis vulgaris. From March 2014 to November 2015, 194 patients with psoriasis vulgaris (102 patients in progressive stage and 92 patients in stable stage) were selected as the case group and 175 healthy people as a control group were enrolled in this study. ELISA was used to detect the levels of IL-17 and VEGF in serum. The qRT-PCR assay was performed to detect the relative expression of miR-143 in PBMCs...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879789/a-review-article-on-brodalumab-in-the-treatment-of-moderate-to-severe-plaque-psoriasis
#12
Omid Roostaeyan, Dario Kivelevitch, Alan Menter
Psoriasis is a chronic immune-mediated skin disorder affecting approximately 2-3% of the worldwide population. Recent advances in our understanding of the immunopathogenesis of psoriasis have resulted in novel therapeutic agents. IL-17, a pro-inflammatory cytokine, plays a pivotal role in psoriasis. Therapeutic agents targeting this cytokine have shown clinical effectiveness in the treatment of moderate-to-severe plaque psoriasis. Brodalumab, a human antibody against IL-17 receptor A, has been approved by the US FDA in February 2017, by the Japanese Pharmaceuticals and Medical Devices Agency in July 2016 and by the EMA in July 2017 for the treatment of moderate-to-severe psoriasis...
September 7, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28870465/inhibition-of-il-17-committed-t-cells-in-a-murine-psoriasis-model-by-a-vitamin-d-analogue
#13
Nobuhiro Kusuba, Akihiko Kitoh, Teruki Dainichi, Tetsuya Honda, Atsushi Otsuka, Gyohei Egawa, Saeko Nakajima, Yoshiki Miyachi, Kenji Kabashima
BACKGROUND: A better understanding of the means by which topical vitamin D analogues exert their therapeutic effect on psoriasis is of theoretical and practical importance. OBJECTIVE: We sought to clarify whether and how the topical vitamin D analogue calcipotriol (CAL) controls the IL-17A-mediated pathogenesis of murine psoriasis-like dermatitis in vivo. METHODS: Psoriasis-like dermatitis was induced by the topical application of an imiquimod (IMQ)-containing cream on the murine ear for 4 to 6 consecutive days...
September 1, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28869867/atopic-dermatitis-and-psoriasis-two-different-immune-diseases-or-one-spectrum
#14
REVIEW
Emma Guttman-Yassky, James G Krueger
Psoriasis and atopic dermatitis (AD) are common T-cell mediated inflammatory diseases of the skin that can be treated by specific cytokine antagonists or more broad immunosuppressive drugs. The diseases are similar in that epidermal keratinocytes respond to T-cell derived cytokines by altering growth and differentiation responses, accounting for major parts of the overall disease phenotype. When studied across European-American populations, psoriasis and AD display differing T-cell polarity and different arrays of cytokines...
September 1, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28865459/clinical-efficacy-and-il-17-targeting-mechanism-of-indigo-naturalis-as-a-topical-agent-in-moderate-psoriasis
#15
RANDOMIZED CONTROLLED TRIAL
Hui-Man Cheng, Yang-Chang Wu, Qingmin Wang, Michael Song, Jackson Wu, Dion Chen, Katherine Li, Eric Wadman, Shung-Te Kao, Tsai-Chung Li, Francisco Leon, Karen Hayden, Carrie Brodmerkel, C Chris Huang
BACKGROUND: Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways. METHODS: A randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24)...
September 2, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28853491/differential-diagnosis-of-palmoplantar-eczema-in-psoriatico-chronic-allergic-contact-dermatitis-and-or-psoriasis
#16
Malgorzata Kolesnik, Ingolf Franke, Anke Lux, Sven R Quist, Harald P Gollnick
Differential diagnosis of palmoplantar non-pustular psoriasis and chronic allergic contact dermatitis (ACD) and the combination of these conditions, termed "eczema in psoriatico" (EIP), is difficult, especially in cases of isolated involvement. A blind re-evaluation of 63 archived formalin-fixed palmoplantar samples, previously diagnosed clinically as either psoriasis or chronic ACD, was performed. Samples were allocated to histopathological diagnoses of psoriasis, contact dermatitis or EIP. Immunohistological stainings were performed for better characterization...
August 30, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28830649/identification-of-an-imidazopyridine-scaffold-to-generate-potent-and-selective-tyk2-inhibitors-that-demonstrate-activity-in-an-in-vivo-psoriasis-model
#17
Jun Liang, Anne Van Abbema, Mercedesz Balazs, Kathy Barrett, Leo Berezhkovsky, Wade S Blair, Christine Chang, Donnie Delarosa, Jason DeVoss, Jim Driscoll, Charles Eigenbrot, Simon Goodacre, Nico Ghilardi, Calum MacLeod, Adam Johnson, Pawan Bir Kohli, Yingjie Lai, Zhonghua Lin, Priscilla Mantik, Kapil Menghrajani, Hieu Nguyen, Ivan Peng, Amy Sambrone, Steven Shia, Jan Smith, Sue Sohn, Vickie Tsui, Mark Ultsch, Karen Williams, Lawren C Wu, Wenqian Yang, Birong Zhang, Steven Magnuson
Herein we report identification of an imidazopyridine class of potent and selective TYK2 inhibitors, exemplified by prototype 6, through constraint of the rotatable amide bond connecting the pyridine and aryl rings of compound 1. Further optimization led to generation of compound 30 that potently inhibits the TYK2 enzyme and the IL-23 pathway in cells, exhibits selectivity against cellular JAK2 activity, and has good pharmacokinetic properties. In mice, compound 30 demonstrated dose-dependent reduction of IL-17 production in a PK/PD model as well as in an imiquimod-induced psoriasis model...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28827714/the-human-il-17a-f-heterodimer-a-two-faced-cytokine-with-unique-receptor-recognition-properties
#18
Arnaud Goepfert, Sylvie Lehmann, Emmanuelle Wirth, Jean-Michel Rondeau
IL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriatic arthritis patients. IL-17A and IL-17F are homodimeric cytokines that can also form the IL-17A/F heterodimer whose precise role in health and disease remains elusive. All three cytokines signal through the assembly of a ternary complex with the IL-17RA and IL-17RC receptors...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28825875/monoclonal-antibodies-inhibiting-il-12-23-and-17-for-the-treatment-of-psoriasis
#19
Caleb Jeon, Sahil Sekhon, Di Yan, Ladan Afifi, Mio Nakamura, Tina Bhutani
Psoriasis is a chronic, inflammatory, immune-mediated skin condition that affects 3 to 4% of the adult U.S. population, characterized by well-demarcated, erythematous plaques with silver scale. Psoriasis is associated with many comorbidities including cardiometabolic disease and can have a negative impact on quality of life. The current armamentarium of psoriasis treatment includes topical therapies, phototherapy, oral immunosuppressive therapies, and biologic agents. Over the past two decades, there has been rapid development of novel biologic therapies for the treatment of moderate-to-severe plaque psoriasis...
August 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28819723/guselkumab-first-global-approval
#20
Anthony Markham
Guselkumab (Tremfya™) is a human monoclonal IgG1λ antibody being developed by Janssen Biotech, Inc. that has been approved in the USA as a treatment for moderate-to-severe plaque psoriasis. Guselkumab inhibits the binding of interleukin 23 (IL-23) to its cell surface receptor, disrupting the type 17 helper T cell/IL-17 pathway. This article summarizes the milestones in the development of guselkumab leading to this first approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy...
August 17, 2017: Drugs
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