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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/29665498/glabridin-an-isoflavan-from-licorice-root-ameliorates-imiquimod-induced-psoriasis-like-inflammation-of-balb-c-mice
#1
Penghui Li, Yonglian Li, Hong Jiang, Yuting Xu, Xiaoying Liu, Biao Che, Jian Tang, Guangrong Liu, Yadong Tang, Wei Zhou, Langyue Zhang, Changzhi Dong, Huixiong Chen, Kun Zhang, Zhiyun Du
In this paper, we investigate the effect of glabridin (Glab) on psoriasis. We observed that Glab significantly suppressed the levels of nitric oxide (NO), NF-κB subunit p65, interleukin (IL)-6, and IL-1β in lipopolysaccharide (LPS)-stimulated HaCaT cells. In addition, Glab treatment reduced the expression of IL-17A, IL-22, and IL-23 in TNF-α-stimulated-HaCaT cells. These findings prompted us to test whether Glab could be used to treat psoriasis in vivo. The effects of Glab on PASI scores, histopathological changes, oxidative/anti-oxidative indexes and pro-inflammatory cytokines in IMQ-induced mice were investigated...
April 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29663834/murine-models-of-psoriasis-and-their-usefulness-for-drug-discovery
#2
Shih-Yi Chuang, Chih-Hung Lin, Calvin T Sung, Jia-You Fang
Psoriasis is an autoimmune skin disease characterized by red plaques with silver or white multilayered scales with a thickened acanthotic epidermis. Using mouse models of cutaneous inflammation, IL-23/Th17 was identified to have a potential key role in psoriasis. New treatments to slow this inflammatory skin disorder are urgently needed. To aid their discovery, a psoriasis animal model mimicking human psoriasis is urgently needed for their early preclinical evaluation. Areas covered: The authors review animal models of psoriasis and analyze the features and molecular mechanisms involved in these mouse models...
April 17, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29655588/resident-and-monocyte-derived-langerhans-cells-are-required-for-imiquimod-induced-psoriasis-like-dermatitis-model
#3
Minseok Lee, Sung Hee Kim, Tae-Gyun Kim, Jeyun Park, Jae Won Lee, Min-Geol Lee
BACKGROUND: Langerhans cells (LCs) are dendritic cells that reside in the epidermis and local inflammation results in an increased differentiation of monocyte-derived LCs. Only few studies have investigated on the role of LCs in psoriasis-like dermatitis model, but the results are variable and the exact role of LCs in psoriasis model remains to be elucidated. OBJECTIVE: To explore the functional role of resident (rLCs) and monocyte-derived LCs (mLCs) in imiquimod (IMQ)-induced psoriasis-like inflammation using human Langerin-diphtheria toxin subunit A (huLang-DTA) mice...
April 6, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29650963/epigenetic-control-of-il-23-expression-in-keratinocytes-is-important-for-chronic-skin-inflammation
#4
Hui Li, Qi Yao, Alberto Garcia Mariscal, Xudong Wu, Justus Hülse, Esben Pedersen, Kristian Helin, Ari Waisman, Caroline Vinkel, Simon Francis Thomsen, Alexandra Avgustinova, Salvador Aznar Benitah, Paola Lovato, Hanne Norsgaard, Mette Sidsel Mortensen, Lone Veng, Björn Rozell, Cord Brakebusch
The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17 cytokine axis. Although IL-23 is expressed by psoriatic keratinocytes and immune cells, only the immune cell-derived IL-23 is believed to be disease relevant. Here we use a genetic mouse model to show that keratinocyte-produced IL-23 is sufficient to cause a chronic skin inflammation with an IL-17 profile. Furthermore, we reveal a cell-autonomous nuclear function for the actin polymerizing molecule N-WASP, which controls IL-23 expression in keratinocytes by regulating the degradation of the histone methyltransferases G9a and GLP, and H3K9 dimethylation of the IL-23 promoter...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29619073/antipsoriatic-effects-of-wannachawee-recipe-on-imiquimod-induced-psoriasis-like-dermatitis-in-balb-c-mice
#5
Mingkwan Na Takuathung, Ariyaphong Wongnoppavich, Ampai Panthong, Parirat Khonsung, Natthakarn Chiranthanut, Noppamas Soonthornchareonnon, Seewaboon Sireeratawong
Psoriasis is a common immune-mediated chronic inflammatory skin disease characterized by thick and erythema raised plaques with adherent silvery scales. T-cells are activated via the IL-23/Th17 axis which is involved in psoriasis pathogenesis. Conventional treatments of psoriasis have adverse events that influence patients' adherence. Wannachawee Recipe (WCR) is Thai traditional medicine that is known to be effective for psoriasis patients; however, preclinical evidence is still lacking. This study investigated the therapeutic potential of WCR on antiproliferant activity using imiquimod- (IMQ-) induced psoriasis-like dermatitis in a mouse model...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29615641/maresin-1-suppresses-imiquimod-induced-skin-inflammation-by-regulating-il-23-receptor-expression
#6
Natsuko Saito-Sasaki, Yu Sawada, Emi Mashima, Takashi Yamaguchi, Shun Ohmori, Haruna Yoshioka, Sanehito Haruyama, Etsuko Okada, Motonobu Nakamura
The anti-inflammatory effect of omega 3 polyunsaturated fatty acids has been confirmed in various inflammatory disease models. Maresin-1 (MaR1) is a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid (DHA) that has displayed strong anti-inflammatory effects in various inflammatory disease models. However, the effect of topical MaR1 on cutaneous inflammation remains unclear. Therefore, we initially examined the anti-inflammatory effects of topical Maresin-1 using an imiquimod (IMQ)-induced psoriasis-like mouse model of inflammation...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29593650/hypophysitis-following-treatment-with-ustekinumab-radiological-and-pathological-findings
#7
Ana M Ramos-Leví, Manuel Gargallo, Ana Serrano-Somavilla, Miguel A Sampedro-Núñez, Javier Fraga, Monica Marazuela
Context: Ustekinumab is a human IgG1 monoclonal antibody that targets interleukin (IL)-12 and IL-23, which may be useful in the treatment of autoimmune conditions such as psoriasis, psoriatic arthritis, and Crohn's disease. Hypophysitis is an immune-derived inflammatory condition of the pituitary gland that may lead to pituitary dysfunction. With the increasing use of immunotherapy, it is possible that this and other new immune-related adverse events (IRAEs) arise, although the mechanisms involved are still incompletely defined...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29588152/generation-and-characterization-of-a-potent-fully-human-monoclonal-antibody-against-the-interleukin-23-receptor
#8
Haruna Sasaki-Iwaoka, Makoto Ohori, Akira Imasato, Katsunari Taguchi, Kyoko Minoura, Tetsu Saito, Kiyoshi Kushima, Emiko Imamura, Satoshi Kubo, Shigetada Furukawa, Tatsuaki Morokata
Interleukin (IL)-12 and IL-23 share a common subunit (p40) and function in T-helper (Th) 1 and Th17 immunity, respectively. Anti-IL-12/23p40 and specific anti-IL-23 antibodies are currently in clinical use for psoriasis and undergoing trials for autoimmune diseases. Since expression levels of the IL-23 receptor are likely to be much lower than those of IL-23, an anti-IL-23 receptor antibody might offer greater promise in inhibiting the IL-23-IL-17 pathways involved in inflammatory disorders. To our knowledge, no anti-IL-23 receptor antibody has been trialed in clinical studies to date...
March 24, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29579456/targeting-the-plasticity-of-psoriasis
#9
Jack L Arbiser, Justin Elsey
Psoriasis is a common inflammatory condition found in 1-2% of the population. The greatest advances in psoriasis treatment have occurred in patients with severe psoriasis, moving from systemic small molecules including methotrexate, cyclosporine, and retinoids to targeted agents against psoriasis-associated cytokines, such as TNF-α, IL-12, IL-23, and IL-17. Although the new biologics do not have the same adverse effects as the systemic drugs, they do predispose to systemic infections (and perhaps cancer), and they are extremely expensive...
April 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29557200/new-therapies-versus-first-generation-biologic-drugs-in-psoriasis-a-review-of-adverse-events-and-their-management
#10
J M Carrascosa, E Del-Alcazar
Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy...
March 20, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29553077/-daily-life-style-and-psoriasis
#11
Yu Sawada, Motonobu Nakamura
Skin is an important organ that is located on the outermost layer of the human body, and serves as a defense barrier against external stimulation. Daily life style, including diet, exercise, and sleep, is a fundamental behavior of humans, and it has recently been reported that daily life style has a strong relationship with the inflammatory condition of skin diseases. This relationship has been examined by various approaches, including epidemiological investigations. Psoriasis is one inflammatory skin disease and is especially closely related with daily life style, such as diet, sleep, smoking and alcohol consumption...
2018: Journal of UOEH
https://www.readbyqxmd.com/read/29549597/biosimilar-drugs-for-psoriasis-principles-present-and-near-future
#12
REVIEW
Jose-Manuel Carrascosa, Ira Jacobs, Danielle Petersel, Robert Strohal
Psoriasis is a chronic, inflammatory, lifelong disease with a high prevalence (afflicting approximately 1-5% of the population worldwide) and is associated with significant morbidity. The introduction of biologic therapies has improved the management of this disease. Multiple biologic medicines that block cytokine signaling, including tumor necrosis factor (TNF) antagonists (adalimumab, etanercept, and infliximab) and inhibitors of interleukin (IL)-17 (brodalumab, ixekizumab, and secukinumab), IL-23 (guselkumab), or IL-12/23 (ustekinumab), are approved for the treatment of psoriasis...
March 16, 2018: Dermatology and Therapy
https://www.readbyqxmd.com/read/29544684/anti-il-12-il-23p40-antibody-ameliorates-dermatitis-and-skin-barrier-dysfunction-in-mice-with-imiquimod-induced-psoriasis-like-dermatitis
#13
Takehiro Takahashi, Yoko Koga, Mie Kainoh
Psoriasis is a chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales, and keratinocyte hyperproliferation. While the cause of psoriasis is not clearly understood, a dysregulated immune system, especially activation of IL-23/IL-17 axis, has been strongly implicated in the pathogenesis of psoriasis. For example, anti-IL-23 therapy is effective in psoriasis patients, and thus IL-23 is considered as a potential therapeutic target for the treatment of psoriasis. The skin barrier provides protection of the human body against infection from external pathogens...
March 12, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29535706/il-36%C3%AE-is-a-strong-inducer-of-il-23-in-psoriatic-cells-and-activates-angiogenesis
#14
Charlie Bridgewood, Gareth W Fearnley, Anna Berekmeri, Philip Laws, Tom Macleod, Sreenivasan Ponnambalam, Martin Stacey, Anne Graham, Miriam Wittmann
The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29535261/p38%C3%AE-signaling-in-langerhans-cells-promotes-the-development-of-il-17-producing-t-cells-and-psoriasiform-skin-inflammation
#15
Tingting Zheng, Weiheng Zhao, Hongjin Li, Shuxiu Xiao, Ran Hu, Miaomiao Han, Heng Liu, Yeqiang Liu, Kinya Otsu, Xinguang Liu, Gonghua Huang
Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38α activity in Langerhans cells (LCs), a skin-resident subset of DCs, promoted the generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease. Deletion of p38α in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell-mediated psoriasiform skin inflammation in mice. The activity of p38α in LCs specifically promoted IL-17 production from γδ and CD4+ T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion...
March 13, 2018: Science Signaling
https://www.readbyqxmd.com/read/29532693/a-systematic-review-and-meta-analysis-of-the-efficacy-and-safety-of-the-interleukin-il-12-23-and-il-17-inhibitors-ustekinumab-secukinumab-ixekizumab-brodalumab-guselkumab-and-tildrakizumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis
#16
Jawad Bilal, Adam Berlinberg, Sandipan Bhattacharjee, Jaren Trost, Irbaz Bin Riaz, Drew J B Kurtzman
OBJECTIVE: To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. METHODS AND RESULTS: 24 randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82-29.54, p < 0.00001) and 14.55 (10.42-20.31, p < 0.00001) for ustekinumab 90mg, 13.75 (8.49-22.28, p < 0...
March 13, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29521875/cytokines-in-uveitis
#17
Jessica E Weinstein, Kathryn L Pepple
PURPOSE OF REVIEW: Increasing evidence supports Th17 cells as key mediators of ocular inflammatory disease. Cytokines that are important for the development and pathologic function of these cells are potential therapeutic targets in patients with immune mediated uveitis. This review provides an overview of these cytokines including recent insights about their roles in ocular inflammation from laboratory and clinical studies. RECENT FINDINGS: Interleukin (IL)-6, IL-10, IL-17, IL-22, IL-23 and tumour necrosis factor-alpha (TNFα) are cytokines that have been examined for their functional role in uveitis and their relationship to pathologic Th17 cells...
March 6, 2018: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/29510001/pharmacokinetics-of-tildrakizumab-mk-3222-an-anti-il-23-monoclonal-antibody-following-intravenous-or-subcutaneous-administration-in-healthy-subjects
#18
Sauzanne Khalilieh, Peter Hodsman, Christine Xu, Anjela Tzontcheva, Shirley Glasgow, Diana Montgomery
Tildrakizumab, a high-affinity humanized IgG1k antibody that selectively binds interleukin (IL)-23 p19 subunit of cytokine IL-23 and neutralizes its function, is under investigation for treatment of moderate-to-severe chronic plaque psoriasis. The objective of this analysis was to assess the pharmacokinetics (PK), bioavailability and safety/tolerability of single ascending doses of tildrakizumab following intravenous (IV) and subcutaneous (SC) dosing in healthy subjects. P05661 was a phase 1, single dose, randomized, placebo-controlled study of tildrakizumab IV doses of 0...
March 6, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29508278/il-23-induced-macrophage-polarization-and-its-pathological-roles-in-mice-with-imiquimod-induced-psoriasis
#19
Yuzhu Hou, Linnan Zhu, Hongling Tian, Hai-Xi Sun, Ruoyu Wang, Lianfeng Zhang, Yong Zhao
Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry...
March 5, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29482382/guselkumab-for-the-treatment-of-psoriasis
#20
Matteo Megna, Anna Balato, Annunziata Raimondo, Nicola Balato
Psoriasis is a chronic immune mediated disease in which the interplay of T cells and keratinocytes seems to play a key role. In this context, the interleukin (IL)-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis and the selective inhibition of IL-23 may be viewed as an improvement of treatments blocking both IL-23 and IL-12, since its upstream actions. Areas covered: The authors performed a thorough and updated review on guselkumab, a fully human IgG1λ monoclonal antibody that blocks the p19 subunit of IL-23, analyzing efficacy and safety data from phase I, II and III trials...
April 2018: Expert Opinion on Biological Therapy
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