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IL-17 and psoriasis

Martina Gatzka
Tumor necrosis factor alpha (TNF-α) and Interleukin 17 (IL-17) are key cytokines driving psoriasis and other inflammatory autoimmune diseases and thus represent effective targets for anti-psoriatic therapy. In a recent issue of The Journal of Pathology, Leite Dantas et al. explore a mouse model of TNF-mediated psoriasiform dermatitis and arthritis with Doxycyclin-inducible general over-expression of human TNF (ihTNFtg mice) for the contributions of macrophages and T cells in skin inflammation - with some unexpected and interesting findings...
October 17, 2016: Journal of Pathology
Philip Mease, Iain B McInnes
INTRODUCTION: Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required. OBJECTIVES: The interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides...
June 2016: Rheumatol Ther
Robert Bissonnette, Judilyn Fuentes-Duculan, Shunya Mashiko, Xuan Li, Kathleen M Bonifacio, Inna Cueto, Mayte Suárez-Fariñas, Catherine Maari, Chantal Bolduc, Simon Nigen, Marika Sarfati, James G Krueger
BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. OBJECTIVE: Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). METHODS: Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects...
September 29, 2016: Journal of Dermatological Science
Iain Welsby, Stanislas Goriely
Interleukin (IL)-23 plays a central role in the orchestration of inflammatory responses. Produced by dendritic cells and macrophages, this cytokine promotes the protection of the host against mucosal pathogens through the induction of IL-17 and related cytokines by lymphoid cells. Preclinical disease models and association studies in humans have also clearly demonstrated the implication of IL-23 signalling pathway in inflammatory diseases. Indeed, this cytokine is now considered as a major therapeutic target in immune-based pathologies such as psoriasis, ankylosing spondylitis or Crohn's disease...
2016: Advances in Experimental Medicine and Biology
Mikiro Takaishi, Masayuki Ishizaki, Keisuke Suzuki, Takashi Isobe, Takaichi Shimozato, Shigetoshi Sano
BACKGROUND: Targeting the IL-17 pathway represents a highly effective strategy for the treatment of psoriasis, using antibodies against IL-17A and IL-17 receptor, suggesting that Th17 cells essentially contribute to development of psoriasis. Th17 differentiation depends on the key transcription factor, RORγt. OBJECTIVE: To develop a novel RORγt antagonist which is effective on psoriasis via oral administration. METHODS: A chemical library was screened using cell-based high-throughput methods, luciferase reporter assay, competitive binding assay, and T cell differentiation assay...
October 3, 2016: Journal of Dermatological Science
Anjali Jain, Sindhu Doppalapudi, Abraham J Domb, Wahid Khan
Psoriasis is an autoimmune skin disorder characterized by hyper proliferation and poor differentiation of keratinocyte. It significantly affects patient's quality of life. This study reports the anti-psoriatic efficacy of tacrolimus and curcumin loaded liposphere gel formulation. Poor solubility, poor skin penetration and erratic absorption are some problems associated with the topical delivery of these drugs. To overcome these problems, lipospheres containing combination of tacrolimus and curcumin was prepared with a particle size of nearly 50nm and incorporated into a gel for topical application...
October 7, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
M Galluzzo, S D'Adamio, L Bianchi, M Talamonti
Psoriasis is a complex disease in which the alteration of the IL-23/Th17 axis appears to be crucial for its pathogenic mechanisms, and anti-IL17 agents are rapidly becoming important therapeutic tools. Brodalumab, a fully human Chinese hamster ovary cell-derived immunoglobulin G2 (IgG2) anti-IL-17RA monoclonal antibody, is currently the most-developed treatment that binds to the IL-17RA. The authors review and provide updates of efficacy and safety by several studies on brodalumab. Areas covered: A PubMed search was performed for relevant literature...
October 10, 2016: Expert Review of Clinical Immunology
Chao Luan, Xu Chen, Yu Hu, Zhimin Hao, Jared M Osland, Xundi Chen, Skyler D Gerber, Min Chen, Heng Gu
Nuclear receptor interacting protein 1 (NRIP1, also known as RIP140) is a co-regulator for various transcriptional factors and nuclear receptors, and has been shown to take part in many biological and pathological processes, such as regulating mammary gland development and inflammatory response.The aim of this study is to investigate the expression of NRIP1 and to explore its roles in the pathogenesis of psoriasis. Thirty active psoriasis patients and 16 healthy volunteers were enrolled for this study. qRT-PCR analyses found that both NRIP1 and RelA/p65 were elevated in psoriatic lesions compared to psoriatic non-lesions and normal controls, and also overexpressed in peripheral blood mononuclear cell (PBMCs) of psoriasis patients...
September 30, 2016: Oncotarget
Agnieszka Owczarczyk-Saczonek, Waldemar Placek
Psoriasis is a systemic disease with numerous concomitant metabolic disorders. Apparently, T-helper 17 lymphocytes and interleukin (IL)-17 constitute an important element linking those disorders. The role of IL-17 has been confirmed by numerous studies, although it remains not completely understood, and the study results are controversial. Based on the studies performed so far, it is assumed that IL-17 contributes to development of atherosclerosis by means of: stimulation of production of proinflammatory compounds; induction of apoptosis of endothelial cells and heart muscle cells; stimulation of von Willebrand factor production; and induction of the matrix metalloproteinase-9 (atherosclerotic plaque rupture)...
October 1, 2016: International Journal of Dermatology
Wang Sin Gina Tan, Stephen Kelly, Constantino Pitzalis
Biologic therapy has revolutionized treatment pathways in psoriatic joint and skin disease. It has also provided a useful tool with which pathological pathways of this condition may be explored. Areas Covered: This review presents data on the clinical and biological effects of targeted therapy in psoriatic arthritis and psoriasis. Therapeutic agents covered include inhibitors of TNFα, inhibitors of the IL-23/IL-17 axis and inhibitors of intracellular small molecules involved in the transduction of the inflammatory signal...
October 3, 2016: Expert Review of Clinical Immunology
Trang T Vu H, Melinda Gooderham, Kim Papp
The interleukin (IL)-17 family of cytokines has emerged as an important pro-inflammatory mediator of psoriasis and psoriatic arthritis (PsA). Ixekizumab is an IL17A inhibitor that has been approved for the treatment of chronic plaque psoriasis. Phase III studies of ixekizumab in treating of PsA demonstrated promise by minimizing disease severity and progression. Areas covered: This review focuses on the biologic properties, pharmacokinetics and key clinical trial results that demonstrated the safety and efficacy of ixekizumab in treating psoriatic disease...
October 3, 2016: Expert Review of Clinical Pharmacology
Molly Campa, Alan Menter
INTRODUCTION: Interleukin-17 has recently been identified as a key player in the pathogenesis of psoriasis. As such, several drugs targeting IL-17 are in various stages of clinical development. AREAS COVERED: In this review, the authors describe several emerging therapies and drug candidates targeting IL-17. The authors detail many biologic injectable drug candidates as well as numerous potential oral and topical small molecule drug candidates. EXPERT OPINION: Approval of IL-17 inhibitors has significantly improved the treatment options for psoriasis patients...
September 30, 2016: Expert Opinion on Investigational Drugs
Jaehwan Kim, James G Krueger
Psoriasis vulgaris, affecting the skin, is one of the most common organspecific autoimmune diseases in humans. Until recently, psoriasis was treated by agents or approaches discovered largely through serendipity. Many of the available drugs were inherently quite toxic when used as continuous treatment for many years in this chronic disease. However, an increasing understanding of disease-specific immune pathways has spurred development of pathway-targeted therapeutics during the past decade. Psoriasis is now the most effectively treated human autoimmune disease, with high-level clinical improvements possible in ∼90% of patients using a new generation of drugs that selectively target the IL-23/Type 17 T cell axis...
September 23, 2016: Annual Review of Medicine
Sirish K Ippagunta, Ruchika Gangwar, David Finkelstein, Peter Vogel, Stephane Pelletier, Sebastien Gingras, Vanessa Redecke, Hans Häcker
Psoriasis is a chronic inflammatory skin disease with a clear genetic contribution, characterized by keratinocyte proliferation and immune cell infiltration. Various closely interacting cell types, including innate immune cells, T cells, and keratinocytes, are known to contribute to inflammation. Innate immune cells most likely initiate the inflammatory process by secretion of IL-23. IL-23 mediates expansion of T helper 17 (Th17) cells, whose effector functions, including IL-17A, activate keratinocytes. Keratinocyte activation in turn results in cell proliferation and chemokine expression, the latter of which fuels the inflammatory process through further immune cell recruitment...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
A Batalla, E Coto, J Gómez, N Eirís, D González-Fernández, C Gómez-De Castro, E Daudén, M Llamas-Velasco, R Prieto-Perez, F Abad-Santos, G Carretero, F S García, Y B Godoy, L F Cardo, B Alonso, S Iglesias, P Coto-Segura
Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months...
September 27, 2016: Pharmacogenomics Journal
Ka Lun Cheung, Rachael Jarrett, Sumithra Subramaniam, Maryam Salimi, Danuta Gutowska-Owsiak, Yi-Ling Chen, Clare Hardman, Luzheng Xue, Vincenzo Cerundolo, Graham Ogg
Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 response. Yet, it has proved challenging to identify relevant peptide-based T cell antigens. Antigen-presenting Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A2 (PLA2) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells...
September 26, 2016: Journal of Experimental Medicine
Lazaros I Sakkas, Dimitrios P Bogdanos
Psoriatic arthritis (PsA) is a psoriasis (Ps)-associated inflammatory joint disease that affects peripheral joints, entheses, spine, and eyes. PsA and Ps are likely to be the same disease. PsA develops in nearly 70% of patients with Ps, and the hallmark of the disease is bone erosions and bone formation. Both innate and adaptive immunity appear to contribute to pathogenesis of PsA and Ps. Trauma may be a trigger factor for both PsA and Ps. The same T cell clones were reported to be present in both synovial tissues and skin lesions suggesting that a common antigen drives T cell immune response in the joints and skin lesions of patients with PsA...
September 22, 2016: Autoimmunity Reviews
Mariagrazia Granata, Evangelia Skarmoutsou, Chiara Trovato, Giulio A Rossi, Maria Clorinda Mazzarino, Fabio D'Amico
Obesity, type 1 diabetes, and psoriasis are wide-ranging health problems. Genetics, epigenetics, and environmental factors together with immune disturbances are involved in these diseases. The white adipose tissue is an active endocrine organ, secreting a wide variety of soluble mediators called adipokines that have a central role in the relationship between adipose tissue and immune system. Inflammatory cytokines, including the IL-23/IL-17 and IL-18 axes, and microRNAs are involved in many processes, including immunity and inflammation, thus having a major role in the onset of these three diseases...
September 17, 2016: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
Sarah M Bronner, Jason R Zbieg, James J Crawford
INTRODUCTION: The transcription factor RORγ plays a critical role in the expression of pro-inflammatory cytokine interleukin IL-17 and is therefore an attractive target for the treatment of inflammatory diseases. Interest in this molecular target has been heightened by the advancement of orally and topically administered RORγ modulators into clinical trials. AREAS COVERED: The present review seeks to summarize published patent applications from assignee companies that have disclosed Investigational New Drug (IND) filings for small molecule RORγ/RORγt antagonists and inverse agonists...
September 15, 2016: Expert Opinion on Therapeutic Patents
Agnieszka Wasilewska, Marta Winiarska, Małgorzata Olszewska, Lidia Rudnicka
Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment - a fully human monoclonal antibody that targets IL-17A (secukinumab)...
August 2016: Postȩpy Dermatologii i Alergologii
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