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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/28431948/serum-peptides-as-putative-modulators-of-inflammation-in-psoriasis
#1
Tetsuhiko Matsuura, Masaaki Sato, Kouhei Nagai, Toshiyuki Sato, Mitsumi Arito, Kazuki Omoteyama, Naoya Suematsu, Kazuki Okamoto, Tomohiro Kato, Yoshinao Soma, Manae S Kurokawa
BACKGROUND: Psoriasis is a refractory inflammatory disease, however, its pathophysiology is still not fully understood. OBJECTIVE: We tried to identify novel serum peptides associated with the pathophysiology of psoriasis. METHODS: Serum peptides from 24 patients with psoriasis vulgaris (PV), 10 patients with psoriatic arthritis (PsA), 14 patients with atopic dermatitis (AD), and 23 healthy control (HC) subjects were analyzed by mass spectrometry...
March 27, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#2
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signaling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28422002/treatment-of-psoriasis-with-ustekinumab-improved-skin-tightening-in-systemic-sclerosis
#3
Asako Ichihara, Masatoshi Jinnin, Hironobu Ihn
Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by fibrosis, inflammation and vasculopathy in the skin and internal organs. Recently, several articles described that Th17 cells, IL-23 and IL-17 levels were significantly elevated in the peripheral blood or fibrotic sites of SSc. We report a case of SSc and psoriasis administered ustekinumab, IL-12/IL-23 inhibitor. In this case, the skin tightening was successfully improved and ustekinumab was more effective, even though oral prednisolone (9-12 mg/day) had some effect on skin tightening and arthralgia...
April 19, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28414181/myeloid-but-not-plasmacytoid-blood-dcs-possess-th1-polarizing-and-th1-th17-recruiting-capacity-in-psoriasis
#4
Ahmed Khasawneh, Sándor Baráth, Barbara Medgyesi, Gabriella Béke, Zsolt Dajnoki, Krisztián Gáspár, Adrienn Jenei, Lilla Pogácsás, Kitti Pázmándi, János Gaál, Attila Bácsi, Andrea Szegedi, Anikó Kapitány
Psoriasis is a common inflammatory skin disease and dendritic cells (DCs) play crucial role in the development of skin inflammation. Although the characteristics of skin DCs in psoriasis are well defined, less is known about their peripheral blood precursors. Our aim was to characterize the phenotypic features as well as the cytokine and chemokine production of CD1c(+) myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in the blood samples of psoriatic patients. Blood DCs were isolated by using a magnetic separation kit, and their intracytoplasmic cytokine production and CD83/CD86 maturation/activation marker expression were investigated by 8-colour flow cytometry...
April 13, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28390479/the-immunology-of-atopic-dermatitis-and-its-reversibility-with-broad-spectrum-and-targeted-therapies
#5
REVIEW
Patrick M Brunner, Emma Guttman-Yassky, Donald Y M Leung
Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is driven by both terminal keratinocyte differentiation defects and strong type 2 immune responses. In contrast to chronic plaque-type psoriasis, AD is now understood to be a much more heterogeneous disease, with additional activation of TH22, TH17/IL-23, and TH1 cytokine pathways depending on the subtype of the disease. In this review we discuss our current understanding of the AD immune map in both patients with early-onset and those with chronic disease...
April 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28389592/cutting-edge-selective-oral-rock2-inhibitor-reduces-clinical-scores-in-patients-with-psoriasis-vulgaris-and-normalizes-skin-pathology-via-concurrent-regulation-of-il-17-and-il-10
#6
Alexandra Zanin-Zhorov, Jonathan M Weiss, Alissa Trzeciak, Wei Chen, Jingya Zhang, Melanie S Nyuydzefe, Carmen Arencibia, Seetharam Polimera, Olivier Schueller, Judilyn Fuentes-Duculan, Kathleen M Bonifacio, Norma Kunjravia, Inna Cueto, Jennifer Soung, Roy M Fleischmann, Alan Kivitz, Mark Lebwohl, Margarita Nunez, Johnnie Woodson, Shondra L Smith, Robert F West, Mark Berger, James G Krueger, John L Ryan, Samuel D Waksal
Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin...
April 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28377495/rig-i-antiviral-signaling-drives-interleukin-23-production-and-psoriasis-like-skin-disease
#7
Huiyuan Zhu, Fangzhou Lou, Qianqian Yin, Yuanyuan Gao, Yang Sun, Jing Bai, Zhenyao Xu, Zhaoyuan Liu, Wei Cai, Fang Ke, Lingyun Zhang, Hong Zhou, Hong Wang, Gang Wang, Xiang Chen, Hongxin Zhang, Zhugang Wang, Florent Ginhoux, Chuanjian Lu, Bing Su, Honglin Wang
Retinoic acid inducible-gene I (RIG-I) functions as one of the major sensors of RNA viruses. DDX58, which encodes the RIG-I protein, has been newly identified as a susceptibility gene in psoriasis. Here, we show that the activation of RIG-I by 5'ppp-dsRNA, its synthetic ligand, directly causes the production of IL-23 and triggers psoriasis-like skin disease in mice. Repeated injections of IL-23 to the ears failed to induce IL-23 production and a full psoriasis-like skin phenotype, in either germ-free or RIG-I-deficient mice...
April 4, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28370441/adverse-skin-reaction-to-secukinumab
#8
M F Peigottu, M A Montesu
Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting about 1 to 3% of the population worldwide (1). The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including TNF-a inhibitors and interleukin (IL) 12/23 and 17 inhibitors. In 2015, secukinumab was the first IL-17A inhibitor approved for the treatment of moderate-to-severe psoriasis, and more recently for the treatment of ankylosing spondylitis and psoriatic arthritis (2). We report a severe cutaneous reaction to secukinumab that required termination of therapy in a patient non-responder to all biologic drugs approved for the treatment of psoriasis...
March 29, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28339016/paeonol-ameliorates-imiquimod-induced-psoriasis-like-skin-lesions-in-balb-c-mice-by-inhibiting-the-maturation-and-activation-of-dendritic-cells
#9
Yujiao Meng, Mingxing Wang, Xiangjiang Xie, Tingting Di, Jingxia Zhao, Yan Lin, Xiaolong Xu, Ningfei Li, Yating Zhai, Yan Wang, Ping Li
Paeonol, an active component derived from the traditional Chinese medicine Cortex Moutan, possesses anti-inflammatory, analgesic, antioxidant and anti-allergic properties. Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of Toll‑like receptors (TLRs) in dendritic cells (DCs), which are primarily responsible for initiating an immune response. We investigated the effect of paeonol on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by R848...
March 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28329588/ustekinumab-for-treatment-of-cutaneous-crohn-s-disease
#10
Rana Abdat, Alina Markova, Francis A Farraye, Michael K Lichtman
Cutaneous Crohn disease (CD) affecting the vulva, perineum, and perianal skin, is a rare entity, which may accompany or precede gastrointestinal CD. Vulvar involvement, if untreated, may ultimately require extensive surgery including vulvectomy to gain control of the disease. Both gastrointestinal and cutaneous CD respond to biologics, which block TNF. In addition, ustekinumab, which targets both IL-12 and IL-23 cytokines, is effective in patients with gastrointestinal CD who fail TNF blockade. However, it is unclear if ustekinumab is effective for cutaneous CD...
October 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329515/cutaneous-mucinosis-in-a-patient-taking-ustekinumab-for-palmoplantar-psoriasis
#11
Caren Garber, David Rosmarin, Bichchau Nguyen, Mahmoud Goodarzi, Shweta Shinagare, Chad Jessup, Abdulaziz Madani, Shiu-Chung Au, Afnan Hasanain
Discrete papular lichen myxedematosus (DPLM), asubset of localized lichen myxedematosus, is a rarecutaneous mucinosis of unknown etiology. We reporta case of a 57-year-old woman with palmoplantarpsoriasis who developed DPLM 8 weeks after addingustekinumab to a long-term course of methotrexate.The patient had previously failed 2 prior tumor necrosisfactor (TNF) inhibitors, adalimumab and etanercept.This case demonstrates an association between TNFinhibitor and ustekinumab use in a psoriasis patientand localized lichen myxedematosus for the secondtime in the literature...
March 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329405/a-review-of-guselkumab-an-il-23-inhibitor-for-moderate-to-severe-plaque-psoriasis
#12
Z Nawas, M Hatch, E Ramos, M Liu, Y Tong, A Peranteau, S Tyring
Psoriasis is a chronic inflammatory skin disorder that affects 2% of the population. Evidence suggests that interleukin (IL)-23 plays a pivotal role in the pathogenesis of psoriasis. Guselkumab is a subcutaneously administered, humanized anti-IL23 monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis. Data from Phase I-III trials in this patient population reveal that guselkumab has proven to be superior to placebo or adalimumab based on achieving a Psoriasis Area and Severity Index (PASI) 90% reduction, or a static Physician Global Assessment (sPGA) score of 0 or 1 from baseline...
March 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28319618/new-biologics-in-psoriasis-an-update-on-il-23-and-il-17-inhibitors
#13
Joanna Dong, Gary Goldenberg
As immune-related pathways involved in the pathogenesis of psoriasis are elucidated, new biologic treatments targeting these steps of the psoriatic immune cascade are developed. In this article, we review the literature on IL-23 and IL-17 inhibitors in the pipeline for use in moderate to severe psoriasis. Numerous pipeline biologic therapies, including risankizumab, guselkumab, tildrakizumab, ixekizumab, and brodalumab, are being investigated in phase 2 and 3 studies to establish the efficacy and safety of these new agents...
February 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28300862/reversible-posterior-leukoencephalopathy-syndrome-rpls-in-a-psoriasis-patient-treated-with-ustekinumab
#14
Lauren Dickson, Alan Menter
The use of monoclonal antibodies against interleukin (IL)-12 and -23, such as ustekinumab, has considerably reduced the disease burden in many patients with moderate to severe psoriasis. Reversible posterior leukoencephalopathy syndrome (RPLS) is a neurologic disorder that has been documented with increased frequency with the use of systemic and biologic agents. We report a case of a 58-year-old man with psoriasis who presented with confusion and memory difficulties after being on treatment with ustekinumab for over six years...
February 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28299442/interleukin-il-18-cooperatively-with-il-23-induces-prominent-inflammation-and-enhances-psoriasis-like-epidermal-hyperplasia
#15
Noriko Shimoura, Hiroshi Nagai, Susumu Fujiwara, Haruki Jimbo, Takayuki Yoshimoto, Chikako Nishigori
The interleukin (IL)-23/IL-17 axis is strongly implicated in the pathogenesis of psoriasis. Previous studies showed that IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index. However, the mechanism whereby IL-18 affects disease severity remains unknown. In this study, we investigated the effects of IL-18 on a psoriasis-like skin inflammation model induced by recombinant mouse IL-23. We found that IL-18, cooperatively with IL-23, induced prominent inflammation and enhanced psoriasis-like epidermal hyperplasia...
May 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28285360/kynurenic-acid-downregulates-il-17-1l-23-axis-in-vitro
#16
Sanam Salimi Elizei, Malihe-Sadat Poormasjedi-Meibod, Xia Wang, Maryam Kheirandish, Aziz Ghahary
Exploring the function of interleukin (IL) 17 and related cytokine interactions have been proven useful toward understanding the role of inflammation in autoimmune diseases. Production of the inflammatory cytokine IL-23 by dendritic cells (DC's) has been shown to promote IL-17 expression by Th17 cells. It is well established that Th17 cells play an important role in several autoimmune diseases including psoriasis and alopecia. Our recent investigations have suggested that Kynurenine-rich environment can shift a pro-inflammatory response to an anti-inflammatory response, as is the case in the presence of the enzyme Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation and Kynurenine (Kyn) production...
March 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28276258/an-interleukin-12-b-single-nucleotide-polymorphism-increases-il-12p40-production-and-is-associated-with-increased-disease-susceptibility-in-patients-with-relapsing-remitting-multiple-sclerosis
#17
Mohammad Reza Javan, Sarieh Shahraki, Amin Safa, Mohammad Reza Zamani, Arash Salmaninejad, Saeed Aslani
BACKGROUND: Through mounting genetic investigations, it has been established that IL12B and IL23R gene single nucleotide polymorphisms have significant associations with autoimmune diseases including inflammatory bowel disease, psoriasis, and ankylosing spondylitis. IL-12/IL-23 pathway plays a pivotal role in etiopathogenesis of multiple sclerosis (MS), suggested by studies both in patients and animal models. METHODS: In a case-control study, 145 MS patients and 200 healthy subjects were genotyped for polymorphisms in IL12B and IL23R genes using Real-Time PCR allelic discrimination approach...
March 9, 2017: Neurological Research
https://www.readbyqxmd.com/read/28271735/tildrakizumab-for-treating-psoriasis
#18
Marco Galluzzo, Simone D'adamio, Luca Bianchi, Marina Talamonti
Agents that block inflammatory pathways other than tumor necrosis factor (TNF) have represented new options for treating psoriasis in recent years. IL-23 is involved in regulating Th17 cells and is a potent activator of keratinocyte proliferation. Targeting IL-23p19 alone may be a promising treatment approach in patients with moderate-to-severe chronic plaque psoriasis, with a downregulation of Th17 and Th22 cell responses, while IL-12 blockade is not required to achieve efficacy in these patients. Areas covered: The authors review and provide an update on tildrakizumab, a humanized IgG1 monoclonal antibody that blocks the p19 subunit of IL-23...
March 17, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28266782/systemic-immune-mechanisms-in-atopic-dermatitis-and-psoriasis-with-implications-for-treatment
#19
REVIEW
Emma Guttman-Yassky, James G Krueger, Mark G Lebwohl
Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases that negatively affect patients' quality of life. Although distinctions exist between these diseases, both are characterised by erythematous, thickened epidermal lesions that vary in intensity and affected body surface area. Early models of etiology attributed symptoms of both diseases to cutaneous inflammation at lesion sites, but recent studies have established that activated immune mediators in the circulation drive disease severity. Activation of T helper 2 (Th2) and Th22 cells in the circulation appears to be the principal initiator of acute AD pathology, with the emergence of Th1 and Th17/interleukin (IL)-23 pathway activation marking the transition to a chronic state...
March 7, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28258057/psoriasis-as-a-human-model-of-disease-to-study-inflammatory-atherogenesis
#20
Charlotte L Harrington, Amit K Dey, Raza Yunus, Aditya A Joshi, Nehal N Mehta
Inflammation is known to play a significant role in the process of atherogenesis and cardiovascular disease (CVD). Indeed, patients with chronic inflammatory diseases are at increased risk for cardiovascular events. The mechanisms linking chronic inflammation and CVD however remain poorly understood. Psoriasis, a chronic inflammatory skin disease associated with a greater risk of early cardiovascular events, provides a suitable human model to study the pathophysiology of inflammatory atherogenesis in humans...
March 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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