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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/28239238/cytokine-imbalance-as-a-common-mechanism-in-both-psoriasis-and-rheumatoid-arthritis
#1
Yong Tan, Qiu Qi, Cheng Lu, Xuyan Niu, Yanping Bai, Chunyan Jiang, Yang Wang, Youwen Zhou, Aiping Lu, Cheng Xiao
Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28239073/effects-of-topical-application-of-betamethasone-on-imiquimod-induced-psoriasis-like-skin-inflammation-in-mice
#2
Hiroki Mori, Kojo Arita, Takayuki Yamaguchi, Midori Hirai, Yoichi Kurebayashi
Psoriasis is a chronic inflammatory skin disease mediated by dysregulated auto-reactive immune system. In this study, in order to confirm and further extend the pharmacological basis of topical steroids in psoriasis therapy, we investigated the effect of betamethasone ointment on imiquimod (IMQ)-induced skin inflammation in mice. In BALB/c mice, topical IMQ at the dose of 250 µg each on both sides of the ear induced marked psoriasis-like skin inflammation within 5 days. The same dose of IMQ produced only slight to moderate skin inflammation even on Day 7 in CB-17 scid mice...
September 9, 2016: Kobe Journal of Medical Sciences
https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#3
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28165883/the-role-of-il-23-in-the-treatment-of-psoriasis
#4
Lluís Puig
The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade...
February 6, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28129604/formula-psori-cm01-inhibits-the-inflammatory-cytokine-and-chemokine-release-in-keratinocytes-via-nf-%C3%AE%C2%BAb-expression
#5
Ling Han, Jing Sun, Chuan-Jian Lu, Rui-Zhi Zhao, Yue Lu, Han-Jie Lin, Jian-An Wei
Psoriasis is a common chronic inflammatory disease in which T-helper 1(Th1) and T-helper 17(Th17) cells play an important role in its pathology. Formula PSORI-CM01 was a novel formulated Chinese medicine used for psoriasis therapy. It had been demonstrated previously that PSORI-CM01 and serum contained Formula PSORI-CM01 (PCM01CS) could improve psoriasis by inhibiting the epithelial hyperplasia, how PSORI-CM01 affects inflammatory cytokine and chemokine in dermis is still unknown. In this study we found PSORI-CM01 pre-treated 3days before IMQ painting could ameliorated IMQ-induced mice skin lesion as PASI score was apparently reduced...
January 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28124315/relevance-of-in-vitro-3-d-skin-models-in-dissecting-cytokine-contribution-to-psoriasis-pathogenesis
#6
REVIEW
A Chiricozzi, M Romanelli, S Panduri, E Donetti, F Prignano
Psoriasis is a chronic skin disease characterized by the activation of various T cell subsets secreting IFNγ, IL-17, and IL-22, dendritic cells producing TNFα and IFNα, and other immune cells including neutrophils and mast cells. Keratinocytes respond to different cytokine signals orchestrating innate and adaptive immune responses. In vitro studies sought to clarify the cytokine effects on keratinocytes in order to evaluate the centrality of these mediators in psoriasis pathogenesis. The aim of this review is to highlight the relevance of this peculiar in vitro approach in investigating cytokine effects on skin or multilayered epidermis...
January 26, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28122092/a-review-of-brodalumab-an-il-17-receptor-antagonist-for-moderate-to-severe-plaque-psoriasis
#7
Y Tong, A J Peranteau, Z Nawas, S K Tyring
Psoriasis is a chronic immune-mediated inflammatory disease with epidermal hyperplasia that affects 2-3% of the population. Interleukin (IL)-17 signaling has a central role in its pathogenesis. Brodalumab is a monoclonal antibody that neutralizes IL-17 receptor type A. Brodalumab is highly effective in the reversal of psoriatic phenotype and gene expression patterns.
January 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28122069/interleukin-23-helper-t-cell-17-axis-as-a-treatment-target-for-pityriasis-rubra-pilaris
#8
Laurence Feldmeyer, Alessio Mylonas, Olivier Demaria, Anna Mennella, Nikhil Yawalkar, Emmanuel Laffitte, Daniel Hohl, Michel Gilliet, Curdin Conrad
Importance: Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. Objective: To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP...
January 25, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28117878/siramesine-causes-preferential-apoptosis-of-mast-cells-in-skin-biopsies-from-psoriatic-lesions
#9
E Hagforsen, M Lampinen, A Paivandy, S Weström, H Velin, S Öberg, G Pejler, O Rollman
BACKGROUND: Skin mast cells are implicated as detrimental effector cells in various inflammatory skin diseases such as contact eczema, atopic dermatitis and psoriasis. Selective reduction of cutaneous mast cells, e.g. by inducing targeted apoptosis, might prove a rational and efficient therapeutic strategy in dermatoses negatively influenced by mast cells. OBJECTIVES: The objective of the present study was to evaluate whether a lysosomotropic agent such as siramesine can cause apoptosis of mast cells present in psoriatic lesions...
January 24, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28110689/cannabinoids-possible-agents-for-treatment-of-psoriasis-via-suppression-of-angiogenesis-and-inflammation
#10
Amir Hossein Norooznezhad, Fatemeh Norooznezhad
Psoriasis is a chronic skin disease also affecting other sites such as joints. This disease highly depends on inflammation and angiogenesis as well as other pathways. At each step of the psoriasis molecular pathway, different inflammatory cytokines and angiogenic growth factors are involved such as hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), matrix metalo proteinases (MMPs), basic fibroblast growth factor (bFGF), Angiopoitin-2, interleukin-8 (IL-8), IL-17, and IL-2. Beside the mentioned growth factors and cytokines, cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which play roles in both angiogenesis and inflammation are also involved in the pathogenesis...
February 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28109175/langerhans-cell-markers-cd1a-and-cd207-are-the-most-rapidly-responding-genes-in-lesional-psoriatic-skin-following-adalimumab-treatment
#11
L Raaby, C Rosada, A Langkilde, K L Lauridsen, H Vinter, P Ommen, R B Kjellerup, C Johansen, L Iversen
TNFα-, IL-23- and IL-17-targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin the presence of Langerhans cells (LC) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL-23/IL-17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL-17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air-liquid interphase for 4 days...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28107570/efficacy-and-safety-of-interleukin-17-antagonists-in-patients-with-plaque-psoriasis-a-meta-analysis-from-phase-3-randomized-controlled-trails
#12
Dan Wu, Si-Yuan Hou, Shuai Zhao, Lin-Xin Hou, Ting Jiao, Nan-Nan Xu, Ning Zhang
BACKGROUND: The interleukin-17 (IL-17) cytokine pathway plays a key role in the development of psoriasis. Antibodies targeting IL-17 or blocking its receptor may be a new therapeutic approach for psoriasis. To assist treatment selection in daily practice it is essential to understand the benefit and risk profile of IL-17 antagonists. OBJECTIVE: We performed a meta-analysis to evaluate the efficacy and safety of IL-17 antagonists in patients with psoriasis. METHODS: We searched a number of databases for relevant randomized clinical trials (RCTs) published before May 2016...
January 20, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#13
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28052238/anti-psoriatic-potential-of-solanum-xanthocarpum-stem-in-imiquimod-induced-psoriatic-mice-model
#14
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
#15
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...
February 2017: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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