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Il-23 and psoriasis

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https://www.readbyqxmd.com/read/29926968/effect-of-tildrakizumab-mk-3222-a-high-affinity-selective-anti-il23p19-monoclonal-antibody-on-cytochrome-p450-metabolism-in-subjects-with-moderate-to-severe-psoriasis
#1
S Khalilieh, A Hussain, D Montgomery, V Levine, P M Shaw, I Bodrug, L Mekokishvili, C Bailey-Smith, X S Glasgow, A Cheng, M Martinho, M Iwamoto
AIMS: Tildrakizumab, an interleukin (IL)-23 inhibitor, is indicated for the treatment of moderate to severe chronic plaque psoriasis. Although tildrakizumab is not metabolized by, and does not alter, cytochrome P450 (CYP) expression in vitro, clinically-significant pharmacokinetic effects through changes in systemic inflammation, which alters CYP metabolism, have been well documented. At the time of study conduct, the effect of modulation of inflammation/cytokines, including IL-23 inhibition with tildrakizumab, on CYP metabolism, and therefore the potential for disease-drug interactions, in psoriasis patients was unknown...
June 21, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29922283/whodunit-the-contribution-of-interleukin-il-17-il-22-producing-%C3%AE-%C3%AE-t-cells-%C3%AE-%C3%AE-t-cells-and-innate-lymphoid-cells-to-the-pathogenesis-of-spondyloarthritis
#2
REVIEW
Annika Reinhardt, Immo Prinz
γδ T cells, αβ T cells, and innate lymphoid cells (ILCs) are capable of producing interleukin (IL)-17A, IL-17F, and IL-22. Among these three families of lymphocytes, it is emerging that γδ T cells are, at least in rodents, the main source of these key pro-inflammatory cytokines. γδ T cells were implicated in multiple inflammatory and autoimmune diseases, including psoriasis, experimental autoimmune encephalomyelitis and uveitis, colitis, and rheumatoid arthritis. Recent findings pointed toward a central role of γδ T cells in the pathogenesis of spondyloarthritis (SpA), a group of inflammatory rheumatic diseases affecting the axial skeleton...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29899748/transcription-factor-retinoid-related-orphan-receptor-%C3%AE-t-a-promising-target-for-the-treatment-of-psoriasis
#3
REVIEW
Lipeng Tang, Xiaozhi Yang, Yongxin Liang, Hesong Xie, Zhenhua Dai, Guangjuan Zheng
Psoriasis, which is a common chronic inflammatory skin disease, endangers human health and brings about a major economic burden worldwide. To date, treatments for psoriasis remain unsatisfied because of their clinical limitations and various side effects. Thus, developing a safer and more effective therapy for psoriasis is compelling. Previous studies have explicitly shown that psoriasis is an autoimmune disease that is predominantly mediated by T helper 17 (Th17) cells, which express high levels of interleukin-17 (IL-17) in response to interleukin-23 (IL-23)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29897790/a-safety-evaluation-of-guselkumab-for-the-treatment-of-psoriasis
#4
M Galluzzo, S D'Adamio, E Campione, L Bianchi, M Talamonti
Guselkumab is a fully human monoclonal IgG1λ antibody for the treatment of plaque psoriasis that inhibits interleukin (IL)-23p19 subunit, reducing the proliferation of type 17 helper T (Th-17) cells and thus production of Th-17-derived pro-inflammatory cytokines, especially IL-17 and IL-22. Areas covered: In the following article, the mechanism of action and mainly the efficacy and safety profile of guselkumab available from results of trials will be discussed. We summarized these data after a literature review including PubMed search, relating proceedings and abstracts from relevant international conferences, assessment reports from European and United States regulatory agencies and treatment guidelines up to April 2018...
June 13, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29870687/extracellular-atp-and-il-23-form-a-local-inflammatory-circuit-leading-to-the-development-of-a-neutrophil-dependent-psoriasiform-dermatitis
#5
Julio A Diaz-Perez, Meaghan E Killeen, Yin Yang, Cara D Carey, Louis D Falo, Alicia R Mathers
Psoriasis is a chronic inflammatory skin disease dependent on the IL-23/IL-17 axis, a potent inflammatory pathway involved in pathogen clearance and autoimmunity. Several triggers have been proposed as initiators for psoriasis, including alarmins such as ATP. However, the role of alarmins in psoriasis pathogenesis and cutaneous inflammation has not been well addressed. Herein studies demonstrate that signaling through the P2X7 receptor (P2X7R) pathway underlies the development of psoriasiform inflammation. In this regard, psoriasiform dermatitis induced by IL-23 is dependent on P2X7R signaling...
June 2, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29867905/probiotic-lactobacillus-sakei-probio-65-extract-ameliorates-the-severity-of-imiquimod-induced-psoriasis-like-skin-inflammation-in-a-mouse-model
#6
Irfan A Rather, Vivek K Bajpai, Yun Suk Huh, Young-Kyu Han, Eijaz A Bhat, Jeongheui Lim, Woon K Paek, Yong-Ha Park
This study was designed to evaluate the protective effect of ethanol extract (SEL001) isolated from a potent probiotic strain Lactobacillus sakei proBio-65 on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model. Histopathological and histomorphometrical changes in the ear and dorsal skin tissues were observed under hematoxylin and eosin stain for general histopathological architectures or Masson's trichrome stain for collagen fibers. The expression profile of psoriasis-associated specific genes was determined using Real-Time PCR analysis...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29862305/inhibition-of-il-17-and-il-23-in-human-keratinocytes-by-the-a-3-adenosine-receptor-agonist-piclidenoson
#7
Shira Cohen, Faina Barer, Inbal Itzhak, Michael H Silverman, Pnina Fishman
Interleukin-17 and interleukin-23 play major roles in the inflammatory process in psoriasis. The Gi protein-associated A3 adenosine receptor (A3 AR) is known to be overexpressed in inflammatory cells and in peripheral blood mononuclear cells (PBMCs) of patients with autoimmune inflammatory conditions. Piclidenoson, a selective agonist at the A3 AR, induces robust anti-inflammatory effect in psoriasis patients. In this study, we aimed to explore A3 AR expression levels in psoriasis patients and its role in mediating the anti-inflammatory effect of piclidenoson in human keratinocyte cells...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29859222/acetyl-11-keto-%C3%AE-boswellic-acid-inhibits-the-secretion-of-cytokines-by-dendritic-cells-via-the-tlr7-8-pathway-in-an-imiquimod-induced-psoriasis-mouse-model-and-in-vitro
#8
Ming-Xing Wang, Jing-Xia Zhao, Yu-Jiao Meng, Ting-Ting Di, Xiao-Long Xu, Xiang-Jiang Xie, Yan Lin, Lu Zhang, Ning Wang, Ping Li, Yan Wang
AIMS: Psoriasis vulgaris is mediated by T and dendritic cells. This study aimed to investigate the effects of acetyl-11-keto-β-boswellic acid (AKBA) on activated dendritic cells (DCs) using an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated with resiquimod (R848) in vitro. MATERIALS AND METHODS: The mice were treated with IMQ and intragastrically administered 25-100 mg/kg/day of AKBA, 1 mg/kg/day of methotrexate (MTX), or normal saline...
May 30, 2018: Life Sciences
https://www.readbyqxmd.com/read/29852521/generalized-pustular-psoriasis-a-model-disease-for-specific-targeted-immunotherapy-systematic-review
#9
REVIEW
Alexander Boehner, Alexander A Navarini, Kilian Eyerich
Generalized pustular psoriasis (GPP) psoriasis is a rare, multisystemic skin disease characterized by recurrent episodes of pustulation. GPP can be life-threatening and is often difficult to treat. In the era of precision medicine in dermatology, GPP stands exemplary for both challenges and chances - while new treatments offer great hope, there is urgent need for better definition and stratification of this severe and heterogeneous disease. Our objective was to systematically review the literature for evidence of efficacy of targeted immunotherapy and their mode of action in the context of clinical phenotype, classification and pathogenesis of adult GPP...
May 31, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29802736/clinical-significance-of-decreased-interleukin-35-expression-in-patients-with-psoriasis
#10
Tengda Li, Mingli Gu, Peng Liu, Yun Liu, Jie Guo, Weiwei Zhang, Cheng Qian, Anmei Deng
In psoriasis, a chronic, recurrent, inflammatory skin disease, CD4+T cells and their related cytokines play an important role in its pathogenesis. The role of interleukin (IL)-35, an immunosuppressive cytokine involved in many autoimmune diseases, is unclear in the pathogenesis of psoriasis. This study evaluated IL-35 expression and clinical significance in psoriasis. Protein and mRNA levels of specified markers were measured by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR), respectively...
May 26, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29796240/interleukin-23-in-the-skin-role-in-psoriasis-pathogenesis-and-selective-interleukin-23-blockade-as-treatment
#11
Tom C Chan, Jason E Hawkes, James G Krueger
Plaque psoriasis is one of the most common autoimmune skin diseases and is characterized by erythematous, scaly plaques. Many highly effective, targeted therapies have been developed as a result of an improved understanding of the pathogenesis of psoriasis. Using agents that target the central interleukin (IL)-23/IL-17 immune axis, this once difficult-to-treat disease is now among the most effectively treated autoimmune diseases with major clinical improvements possible in around 90% of patients. In this article, we outline the immune mechanisms responsible for the development of psoriasis and provide an overview of the novel IL-23 antagonists being used to manage this chronic skin disease...
May 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29794016/il-36%C3%AE-from-skin-resident-cells-plays-an-important-role-in-the-pathogenesis-of-imiquimod-induced-psoriasiform-dermatitis-by-forming-a-local-autoamplification-loop
#12
Yuriko Hashiguchi, Rikio Yabe, Soo-Hyun Chung, Masanori A Murayama, Kaori Yoshida, Kenzo Matsuo, Sachiko Kubo, Shinobu Saijo, Yuumi Nakamura, Hiroyuki Matsue, Yoichiro Iwakura
IL-36α (gene symbol Il1f6 ), a member of the IL-36 family, is closely associated with inflammatory diseases, including colitis and psoriasis. In this study, we found that Il1f6 -/- mice developed milder psoriasiform dermatitis upon treatment with imiquimod, a ligand for TLR ligand 7 (TLR7) and TLR8, whereas Il1f6 -/- mice showed similar susceptibility to dextran sodium sulfate-induced colitis to wild-type mice. These effects were observed in both cohoused and separately housed conditions, and antibiotic treatment did not cancel the resistance of Il1f6 -/- mice to imiquimod-induced dermatitis...
May 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29776016/psoriasis-area-and-severity-index-pasi-response-in-moderate-severe-psoriatic-patients-switched-to-adalimumab-results-from-the-oppsa-study
#13
M Talamonti, M Galluzzo, N Bernardini, G Caldarola, S Persechino, F Cantoresi, C G Egan, C Potenza, K Peris, L Bianchi
BACKGROUND: Few studies have compared the efficacy of switching to adalimumab in the real-life setting in plaque psoriasis patients. OBJECTIVE: To evaluate the effect of adalimumab in psoriasis patients previously treated with other biologics. METHODS: In this multicentre study, psoriasis patients (N=262) treated with an anti-TNF alpha agent, ustekinumab or naïve to biologics then switched to adalimumab were included. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 3, 6, 12, 24 and 36 months...
May 18, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29771254/guselkumab-human-monoclonal-antibody-against-interleukin-23-for-moderate-to-severe-psoriasis
#14
D M Paton
Guselkumab is an antibody designed to bind to the p19 subunit of interleukin-23 (IL-23). Detailed studies of affected skin in patients with psoriasis demonstrated that guselkumab induced significant changes in the cellular, cytokine and gene expression profiles of psoriatic lesions accompanied by significant changes in clinical measures of disease activity. The significant clinical response in psoriasis was demonstrated in these studies by significant improvement as reflected in the percentage of patients achieving a Physicians Global Assessment score of 0 or 1, and a 90% or 100% improvement in the Psoriasis Area and Severity Index (PASI 90, PASI 100), as well as changes in quality of life measures...
March 2018: Drugs of Today
https://www.readbyqxmd.com/read/29759005/ido-expressing-fibroblasts-suppress-the-development-of-imiquimod-induced-psoriasis-like-dermatitis
#15
Sanam Salimi Elizei, Mohammadreza Pakyari, Mehraneh Ghoreishi, Ruhangiz Kilani, Sanaz Mahmoudi, Aziz Ghahary
Psoriasis is a chronic skin condition whose pathogenesis is reported to be due to the activation of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Here, we report that indoleamine 2,3-dioxygenase (IDO)-expressing fibroblasts reduce the activity of this pathway in activated immune cells. The findings showed that intralesional injection of IDO-expressing fibroblasts in imiquimod-induced psoriasis-like dermatitis on the back and ear (Pso. ear group) in mice significantly improves the clinical lesional appearance by reducing the number of skin-infiltrated IL-17+ CD4+ T cells (1...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29757188/microrna-210-overexpression-promotes-psoriasis-like-inflammation-by-inducing-th1-and-th17-cell-differentiation
#16
Ruifang Wu, Jinrong Zeng, Jin Yuan, Xinjie Deng, Yi Huang, Lina Chen, Peng Zhang, Huan Feng, Zixin Liu, Zijun Wang, Xiaofei Gao, Haijing Wu, Honglin Wang, Yuwen Su, Ming Zhao, Qianjin Lu
Immune imbalance of T lymphocyte subsets is a hallmark of psoriasis, but the molecular mechanisms underlying this aspect of psoriasis pathology are poorly understood. Here, we report that microRNA-210 (miR-210), a miR that is highly expressed in both psoriasis patients and mouse models, induces helper T (Th) 17 and Th1 cell differentiation but inhibits Th2 differentiation through repressing STAT6 and LYN expression, contributing to several aspects of the immune imbalance in psoriasis. Both miR-210 ablation in mice and inhibition of miR-210 by intradermal injection of antagomir-210 blocked the immune imbalance and the development of psoriasis-like inflammation in an imiquimod-induced or IL-23-induced psoriasis-like mouse model...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29737208/the-immunoregulatory-effects-of-traditional-chinese-medicine-on-psoriasis-via-its-action-on-interleukin-advances-and-considerations
#17
Minfeng Wu, Yu Deng, Su Li, Yu Chen, Dongjie Guo, Xingxiu Jin, Qi Xu, Bin Li, Fulun Li
Psoriasis is a chronic inflammatory cutaneous disease characterized by clinical manifestations of erythema and white scales. The pathogenesis of psoriasis is not yet clear. Despite a combination of hormonal therapy and physiotherapy used in Western medicine, the condition often relapses after withdrawal of drugs. Traditional Chinese medicine (TCM) has therapeutic features and may be a clinically effective formula by regulating unbalanced immune systems, such as by targeting interleukins. In this paper, we review recent research about how Chinese medicine immunoregulates psoriasis via interleukins, and systematically summarizes the related mechanisms...
May 8, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29718027/emerging-therapies-in-psoriasis-a-systematic-review
#18
Erica B Lee, Mina Amin, Tina Bhutani, Jashin J Wu
Many new biologics are being studied for use in psoriasis. In this review, we evaluate and summarize findings about emerging biologic therapies for psoriasis. We reviewed published data from phase 2 and 3 clinical trials of 2 IL-17 inhibitors (ixekizumab and brodalumab); 3 IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab); and 1 tumor necrosis factor (TNF) inhibitor (certolizumab pegol). Janus kinase inhibitors were not included in our review, as they currently are not approved by the US Food and Drug Administration (FDA) and there are no plans to further develop this class for treatment of psoriasis...
March 2018: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/29704872/inhibition-of-interleukin-12-and-or-interleukin-23-for-treatment-of-psoriasis-what-is-the-evidence-for-an-effect-on-malignancy
#19
Elizabeth N Ergen, Nabiha Yusuf
Immune cells and cytokines play an important role in the pathogenesis of psoriasis. Interleukin 12 (IL-12) and IL-23 promote cellular responses mediated by T cells, which contribute to an inflammatory loop responsible for the induction and maintenance of psoriatic plaques. Antibodies that inhibit IL-12/23 or IL-23 are key treatment options for patients with psoriasis. IL-12 and IL-23 also play a key role in immune responses to infections and tumors. A growing body of information from clinical trials, cohort studies, postmarketing reports, genetic studies, and animal models provides insights into the potential biological relationships between IL-12/23 inhibition and malignancies...
April 28, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29689250/card14-gain-of-function-mutation-alone-is-sufficient-to-drive-il-23-il-17-mediated-psoriasiform-skin-inflammation-in-vivo
#20
Mark Mellett, Barbara Meier, Deepa Mohanan, Rebekka Schairer, Phil Cheng, Takashi K Satoh, Betina Kiefer, Caroline Ospelt, Stephan Nobbe, Margot Thome, Emmanuel Contassot, Lars E French
Rare autosomal dominant mutations in the gene encoding the keratinocyte signaling molecule, Caspase Recruitment Domain-Containing Protein 14 (CARD14), have been associated with an increased susceptibility to psoriasis but the physiological impact of CARD14 gain-of-function mutations remains to be fully determined in vivo. Here, we report that heterozygous mice harboring a CARD14 gain-of-function mutation (Card14ΔE138) spontaneously develop a chronic psoriatic phenotype with characteristic scaling skin lesions, epidermal thickening, keratinocyte hyperproliferation, hyperkeratosis and immune cell infiltration...
April 21, 2018: Journal of Investigative Dermatology
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