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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/28052238/anti-psoriatic-potential-of-solanum-xanthocarpum-stem-in-imiquimod-induced-psoriatic-mice-model
#1
Komal M Parmar, Prakash R Itankar, Apurva Joshi, Satyendra K Prasad
ETHNOPHARMACOLOGICAL RELEVANCE: The plant Solanum xanthocarpum Schrad. & Wendl. (Solanaceae) is one of the members of the dashamula (ten roots) in Ayurvedic system of medicine. The stem and fruits are used as an antipyretic, antiasthmatic and is prescribed in skin infections and for relief in burning sensation in the feet accompanied by vesicular eruptions. OBJECTIVE: To scientifically validate the anti-psoriatic potential of Solanum xanthocarpum stem in Imiquimod-induced psoriatic mice model MATERIALS AND METHODS: Ethanolic stems extract of Solanum xanthocarpum (ESX) was first subjected to phytochemical screening and quantification of identified phytoconstituents, which was further standardized with the help of HPTLC using chlorogenic acid as a marker...
January 1, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28027921/t-helper-2-cytokine-regulatory-t-cell-gene-polymorphisms-and-their-relation-with-risk-of-psoriasis-in-a-south-indian-tamil-cohort
#2
Sundar Indhumathi, Medha Rajappa, Laxmisha Chandrashekar, Palghat Hariharan Ananthanarayanan, Devinder Mohan Thappa, Vir Singh Negi
BACKGROUND: Psoriasis is known to be associated with an up-regulation of T-helper (Th)-1 & Th-17 cytokines and a relative down-regulation of Th-2 and T-regulatory (T-reg) cytokines. Certain allelic variants of these cytokine genes may alter Th1/Th17 and Th2/T-reg balance and may be associated with the risk of psoriasis. Hence we aimed to determine the association of IL-4 (rs2243250), IL-10 (rs1800871 and rs1800896) and FOXP3 (rs3761548) gene polymorphisms with risk of psoriasis in South Indian Tamils...
December 24, 2016: Human Immunology
https://www.readbyqxmd.com/read/28026823/anti%C3%A2-cytokine-therapy-for-psoriasis-not-only-tnf%C3%A2-%C3%AE-blockers-overview-of-reports-on-the-effectiveness-of-therapy-with-il%C3%A2-12-il%C3%A2-23-and-t-and-b-lymphocyte-inhibitors
#3
Dominika Wcisło-Dziadecka, Martyna Zbiciak, Ligia Brzezińska-Wcisło, Urszula Mazurek
TNF‑α inhibitors - infliximab, etanercept and adalimumab - can be used in the treatment of psoriasis vulgaris and psoriatic arthritis, along with other inhibitors of proinflammatory cytokines, such as interleukin‑12 (IL‑12) and IL‑23. This paper presents the results of research on the use of biological drugs other than the tumor necrosis factor blockers (TNF‑α), namely inhibitors of IL‑12 and IL‑23 (ustekinumab), T‑cell inhibitors (alefacept and efalizumab), B‑cell inhibitors (rituximab), anti‑IL‑17 agents (secukinumab, ixekizumab, and brodalumab) and IL23p19 inhibitors (guselkumab and tildrakizumab)...
December 8, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28011143/dynamic-changes-in-resident-and-infiltrating-epidermal-dendritic-cells-in-active-and-resolved-psoriasis
#4
Elisa Martini, Maria Wiken, Stanley Cheuk, Irène Gallais Sérézal, Faezzah Baharom, Mona Ståhle, Anna Smed-Sörensen, Liv Eidsmo
Epidermal Langerhans cells (LCs) are spatially separated from dermal dendritic cells (DCs) in healthy human skin. In active psoriasis, maintained by local production of IL-23 and IL-17, DCs infiltrate both skin compartments. Here we show that CCR2(+) epidermal DCs (eDCs), phenotypically distinct from dermal DCs, were strictly confined to lesional psoriasis. The eDCs exceeded the number of LCs and displayed high expression of genes involved in neutrophil recruitment and the activation of keratinocytes and T cells...
December 20, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27999243/serum-levels-of-il-10-and-il-22-cytokines-in-patients-with-psoriasis
#5
Mohammad Reza Sobhan, Mahmood Farshchian, Ali Hoseinzadeh, Hamid Reza Ghasemibasir, Ghasem Solgi
BACKGROUND: As a chronic inflammatory condition, psoriasis results from an interaction between genetic and immunologic factors in a predisposing environment. In spite of compelling evidence for the role of T cells and cytokines in psoriasis, interleukin (IL)-10 and IL-22 have not been sufficiently investigated. OBJECTIVE: To assess the serum levels of IL-10 and IL-22 in patients with psoriasis compared to healthy controls. METHODS: A total of 28 patients with psoriasis were compared with 28 age and sex-matched healthy subjects...
December 2016: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/27984714/il-17-blockade-in-psoriasis
#6
Patrick R Burkett, Vijay K Kuchroo
IL-17A both directly induces and synergizes with other cytokines to promote autoimmune tissue inflammation. Secukinumab and ixekizumab are monoclonal antibodies (mAb) that inhibit interleukin-17A. These two agents were recently approved for treatment of psoriasis, and secukinumab is also approved for treatment of two spondyloarthropathies, psoriatic arthritis and ankylosing spondylitis.
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27964879/activation-of-langerhans-cells-promotes-the-inflammation-in-imiquimod-induced-psoriasis-like-dermatitis
#7
Chunying Xiao, Zhenlai Zhu, Shuhong Sun, Jixin Gao, Meng Fu, Yufeng Liu, Gang Wang, Xu Yao, Wei Li
BACKGROUND: Langerhans cells (LCs) are epidermis-resident dendritic cells that sense and mediate stimuli from skin and outside world, and participate in various skin diseases, playing either pro-inflammatory or regulatory roles. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear, and the conclusions of previous studies are controversial. OBJECTIVES: To explore the role of LCs in mouse model of imiquimod (IMQ)-induced psoriasis-like dermatitis using langerin-diphtheria toxin A (DTA) mice that are constitutively deficient in LCs...
December 5, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27957253/increased-levels-of-circulating-platelet-derived-microparticles-in-psoriasis-possible-implications-for-the-associated-cardiovascular-risk
#8
Evangelia Papadavid, Konstantina Diamanti, Aris Spathis, Maria Varoudi, Ioanna Andreadou, Kostas Gravanis, Kostas Theodoropoulos, Petros Karakitsos, John Lekakis, Dimitrios Rigopoulos, Ignatios Ikonomidis
AIM: To evaluate platelet activation markers in psoriasis patients, compared to controls, and investigate their association with the inflammatory burden of psoriasis. METHODS: Forty psoriatic patients without cardiovascular disease, and 12 healthy controls were subjected to measurement of baseline platelet CD62P, CD63 and CD42b expression, platelet-leukocyte complexes, i.e., platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC) and platelet-lymphocyte complexes, and concentrations of platelet-derived microparticles (PMPs) using flow cytometry...
November 26, 2016: World Journal of Cardiology
https://www.readbyqxmd.com/read/27943400/involvement-of-high-mobility-group-box-1-in-imiquimod-induced-psoriasis-like-mice-model
#9
Tao Chen, Li-Xin Fu, Zai-Pei Guo, Bin Yin, Na Cao, Sha Qin
In the previous work, we have indicated that HMGB1, a pro-inflammatory cytokine, is closely associated with the pathogenesis of psoriasis. To further clarify the role of HMGB1 in the pathogenesis of psoriasis, we investigated the direct function of HMGB1 application and HMGB1 blockade in imiquimod (IMQ)-induced psoriatic mouse model in this study. Mice were treated with imiquimod (IMQ) to induce psoriasis-like inflammation, and consecutively injected with recombinant HMGB1 or phosphate-buffered saline (PBS) i...
December 10, 2016: Journal of Dermatology
https://www.readbyqxmd.com/read/27939414/decreased-expression-of-il-27-in-moderate-to-severe-psoriasis-and-its-anti-inflammation-role-in-imiquimod-induced-psoriasis-like-mouse-model
#10
Wenjuan Chen, Yu Gong, Xilin Zhang, Yunlei Tong, Xiuxiu Wang, Chengwen Fei, Hui Xu, Qian Yu, Yao Wang, Yuling Shi
BACKGROUND: Psoriasis is a high-incident T-cell-mediated autoimmune disease mainly affecting the skin. Interleukin (IL)-27 is a novel member of the IL-6/IL-12 cytokine family, which plays a versatile role in the differentiation and function of distinct T cell subsets. Previous studies uncovered that IL-27 promoted the onset of psoriasis through enhancing the differentiation of T helper (Th) 1 cells. However, the role of IL-27 in other psoriasis-related Th lineages, especially Th17 cells, remains elusive...
February 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27934944/overexpression-of-glucocorticoid-induced-leucine-zipper-gilz-increases-susceptibility-to-imiquimod-induced-psoriasis-and-involves-cutaneous-activation-of-tgf-%C3%AE-1
#11
Elena Carceller, Marlies Ballegeer, Julie Deckers, Carlo Riccardi, Stefano Bruscoli, Tino Hochepied, Claude Libert, Paloma Pérez
Psoriasis vulgaris is a chronic inflammatory skin disease affecting millions of people. Its pathophysiology is complex and involves a skin compartment with epidermal and immune cells which produce cytokines, e.g. belonging to the IL-23-Th17-cell axis. Glucocorticoids (GCs) are the most common therapeutics used in cutaneous inflammatory disorders and GC-induced leucine zipper (GILZ) has emerged as a mediator of GCs due to its anti-inflammatory actions, theoretically lacking GC side-effects. We evaluated whether GILZ may provide a better therapeutic index in comparison to GCs during the onset and progression of psoriasis by generating and characterizing a mouse model with generalized overexpression of this protein (GILZ-Tg mice) and the imiquimod (IMQ) psoriasis model...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27925680/association-between-plasma-interleukin-17-levels-and-risk-of-psoriasis-a-meta-analysis
#12
X Y Zhou, J Bao, B Huang, Y Jin
BACKGROUND: Emerging evidence indicates that plasma interleukin (IL)-17 levels may be associated with increased risk of psoriasis, but the individual published results are inconclusive. AIM: To evaluate IL-17 levels in patients with psoriasis using a meta-analysis of studies comparing IL-17 levels in controls and in patients with psoriasis. METHODS: All relevant studies were identified by searching PubMed, Web of Science and MEDLINE databases before 1 November 2015...
December 7, 2016: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/27920272/mcpip1-regnase-1-restricts-il-17a-and-il-17c-dependent-skin-inflammation
#13
Leticia Monin, Johann E Gudjonsson, Erin E Childs, Nilesh Amatya, Xianying Xing, Akash H Verma, Bianca M Coleman, Abhishek V Garg, Meaghan Killeen, Alicia Mathers, Nicole L Ward, Sarah L Gaffen
The IL-17 family cytokines IL-17A and IL-17C drive the pathogenesis of psoriatic skin inflammation, and anti-IL-17A Abs were recently approved to treat human psoriasis. Little is known about mechanisms that restrain IL-17 cytokine-mediated signaling, particularly IL-17C. In this article, we show that the endoribonuclease MCP-1-induced protein 1 (MCPIP1; also known as regnase-1) is markedly upregulated in human psoriatic skin lesions. Similarly, MCPIP1 was overexpressed in the imiquimod (IMQ)-driven mouse model of cutaneous inflammation...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27910156/ixekizumab-treatment-improves-fingernail-psoriasis-in-patients-with-moderate-to-severe-psoriasis-results-from-the-randomized-controlled-and-open-label-phases-of-uncover-3
#14
P van de Kerkhof, L Guenther, A B Gottlieb, M Sebastian, J J Wu, P Foley, A Morita, O Goldblum, L Zhang, J Erickson, S Ball, P Rich
BACKGROUND: Fingernail psoriasis is difficult to treat. OBJECTIVE: The objective was to evaluate the effect of ixekizumab, a monoclonal antibody selectively targeting IL-17A, on fingernail psoriasis. METHODS: This Phase 3, double-blind trial (UNCOVER-3) randomized patients to placebo, etanercept (50-mg twice weekly), or 80 mg ixekizumab as one injection every 4 (IXE Q4W) or 2 weeks (IXE Q2W) after a 160-mg starting dose. At Week 12, ixekizumab patients received open-label IXE Q4W through Week 60; placebo patients received a 160-mg starting ixekizumab dose and etanercept patients a 4-week placebo washout before starting IXE Q4W...
November 5, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27905482/pharmacologic-modulation-of-ror%C3%AE-t-translates-to-efficacy-in-preclinical-and-translational-models-of-psoriasis-and-inflammatory-arthritis
#15
Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27892456/il-12-protects-from-psoriasiform-skin-inflammation
#16
Paulina Kulig, Stephanie Musiol, Sandra Nicole Freiberger, Bettina Schreiner, Gabor Gyülveszi, Giancarlo Russo, Stanislav Pantelyushin, Kenji Kishihara, Francesca Alessandrini, Thomas Kündig, Federica Sallusto, Günther F L Hofbauer, Stefan Haak, Burkhard Becher
Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed γδT (γδT17) cell subset...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27881938/are-interleukin-15-and-22-a-new-pathogenic-factor-in-pustular-palmoplantar-psoriasis
#17
Aleksandra Lesiak, Igor Bednarski, Marta Pałczyńska, Ewelina Kumiszcza, Marzena Kraska-Gacka, Anna Woźniacka, Joanna Narbutt
INTRODUCTION: Pustular palmoplantar psoriasis (PPP) is a rare type of psoriasis affecting mainly distal parts of the limbs. Despite numerous theories about etiology of PPP, the pathogenesis still remains unclear. Recent data indicate that interleukin (IL)-15, IL-17 and IL-22 enhance a proinflammatory response in certain skin inflammatory diseases such as psoriasis and atopic dermatitis. There is also evidence that anti-endomysial (anti-EMA) and anti-gliadin (AGA) antibodies are engaged in PPP development...
October 2016: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/27868150/clinical-efficiency-of-topical-calcipotriol-betamethasone-treatment-in-psoriasis-relies-on-suppression-of-the-inflammatory-tnf%C3%AE-il-23-il-17-axis
#18
Minna E Kubin, Nina Kokkonen, Riitta Palatsi, Päivi M Hägg, Juha P Väyrynen, Virpi Glumoff, Kirsi-Maria Haapasaari, Tiina Hurskainen, Kaisa Tasanen
The effects of topical calcipotriol/betamethasone combination therapy and betamethasone monotherapy on inflammatory T cell numbers and molecular markers were compared in patients with psoriasis. Combination therapy down-regulated the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-23A, IL-17A, S100A7, CCL-20 and interferon (IFN)-γ in skin and TNF-α, IL-6, IL-23A, T-bet and IFN-γ in peripheral blood mononuclear cells (PBMCs). Betamethasone monotherapy had less effect. Expression of FoxP3 in both skin and PBMCs was down-regulated by calcipotriol/betamethasone, but not by betamethasone...
November 21, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27867753/diabetic-wounds-exhibit-decreased-ym1-and-arginase-expression-with-increased-expression-of-il-17-and-il-20
#19
Phillip J Finley, Cory E DeClue, Scott A Sell, Joseph M DeBartolo, Laurie P Shornick
Objective: Impaired wound healing in diabetic (DB) patients is a significant health problem; however, the roles that cytokines and innate immune cells contribute to this impaired healing are not completely understood. Approach: A mouse model was used to compare the innate immune response during DB and normal wound healing. Two 5-mm full-thickness wounds were created on the dorsal skin of BKS.Cg-m+/+Leprdb/J (DB) and C57BL/6 (wild-type) mice. Innate immune cell markers and cytokine mRNA levels were measured in wound biopsies during the first week of healing...
November 1, 2016: Advances in Wound Care
https://www.readbyqxmd.com/read/27859546/first-in-human-randomised-study-of-bimekizumab-a-humanised-monoclonal-antibody-and-selective-dual-inhibitor-of-il-17a-and-il-17%C3%A2-f-in-mild-psoriasis
#20
S Glatt, E Helmer, B Haier, F Strimenopoulou, G Price, P Vajjah, O A Harari, J Lambert, S Shaw
AIMS: Assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab, (formerly UCB4940), a novel humanised monoclonal antibody and dual inhibitor of interleukin (IL)-17A and IL-17 F, in subjects with mild plaque psoriasis. METHODS: Randomised, double-blind, first-in-human study of bimekizumab in 39 subjects who received single-dose intravenous (iv) bimekizumab (8-640 mg) or placebo (NCT02529956). RESULTS: Bimekizumab demonstrated dose-proportional linear PK and was tolerated across the dose range assessed...
November 13, 2016: British Journal of Clinical Pharmacology
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