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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/27910156/ixekizumab-treatment-improves-fingernail-psoriasis-in-patients-with-moderate-to-severe-psoriasis-results-from-the-randomized-controlled-and-open-label-phases-of-uncover-3
#1
P van de Kerkhof, L Guenther, A B Gottlieb, M Sebastian, J J Wu, P Foley, A Morita, O Goldblum, L Zhang, J Erickson, S Ball, P Rich
BACKGROUND: Fingernail psoriasis is difficult to treat. OBJECTIVE: The objective was to evaluate the effect of ixekizumab, a monoclonal antibody selectively targeting IL-17A, on fingernail psoriasis. METHODS: This Phase 3, double-blind trial (UNCOVER-3) randomized patients to placebo, etanercept (50-mg twice weekly), or 80 mg ixekizumab as one injection every 4 (IXE Q4W) or 2 weeks (IXE Q2W) after a 160-mg starting dose. At Week 12, ixekizumab patients received open-label IXE Q4W through Week 60; placebo patients received a 160-mg starting ixekizumab dose and etanercept patients a 4-week placebo washout before starting IXE Q4W...
November 5, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27905482/pharmacologic-modulation-of-ror%C3%AE-t-translates-to-efficacy-in-preclinical-and-translational-models-of-psoriasis-and-inflammatory-arthritis
#2
Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27892456/il-12-protects-from-psoriasiform-skin-inflammation
#3
Paulina Kulig, Stephanie Musiol, Sandra Nicole Freiberger, Bettina Schreiner, Gabor Gyülveszi, Giancarlo Russo, Stanislav Pantelyushin, Kenji Kishihara, Francesca Alessandrini, Thomas Kündig, Federica Sallusto, Günther F L Hofbauer, Stefan Haak, Burkhard Becher
Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed γδT (γδT17) cell subset...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27881938/are-interleukin-15-and-22-a-new-pathogenic-factor-in-pustular-palmoplantar-psoriasis
#4
Aleksandra Lesiak, Igor Bednarski, Marta Pałczyńska, Ewelina Kumiszcza, Marzena Kraska-Gacka, Anna Woźniacka, Joanna Narbutt
INTRODUCTION: Pustular palmoplantar psoriasis (PPP) is a rare type of psoriasis affecting mainly distal parts of the limbs. Despite numerous theories about etiology of PPP, the pathogenesis still remains unclear. Recent data indicate that interleukin (IL)-15, IL-17 and IL-22 enhance a proinflammatory response in certain skin inflammatory diseases such as psoriasis and atopic dermatitis. There is also evidence that anti-endomysial (anti-EMA) and anti-gliadin (AGA) antibodies are engaged in PPP development...
October 2016: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/27868150/clinical-efficiency-of-topical-calcipotriol-betamethasone-treatment-in-psoriasis-relies-on-suppression-of-the-inflammatory-tnf%C3%AE-il-23-il-17-axis
#5
Minna E Kubin, Nina Kokkonen, Riitta Palatsi, Päivi M Hägg, Juha P Väyrynen, Virpi Glumoff, Kirsi-Maria Haapasaari, Tiina Hurskainen, Kaisa Tasanen
The effects of topical calcipotriol/betamethasone combination therapy and betamethasone monotherapy on inflammatory T cell numbers and molecular markers were compared in patients with psoriasis. Combination therapy down-regulated the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-23A, IL-17A, S100A7, CCL-20 and interferon (IFN)-γ in skin and TNF-α, IL-6, IL-23A, T-bet and IFN-γ in peripheral blood mononuclear cells (PBMCs). Betamethasone monotherapy had less effect. Expression of FoxP3 in both skin and PBMCs was down-regulated by calcipotriol/betamethasone, but not by betamethasone...
November 21, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27867753/diabetic-wounds-exhibit-decreased-ym1-and-arginase-expression-with-increased-expression-of-il-17-and-il-20
#6
Phillip J Finley, Cory E DeClue, Scott A Sell, Joseph M DeBartolo, Laurie P Shornick
Objective: Impaired wound healing in diabetic (DB) patients is a significant health problem; however, the roles that cytokines and innate immune cells contribute to this impaired healing are not completely understood. Approach: A mouse model was used to compare the innate immune response during DB and normal wound healing. Two 5-mm full-thickness wounds were created on the dorsal skin of BKS.Cg-m+/+Leprdb/J (DB) and C57BL/6 (wild-type) mice. Innate immune cell markers and cytokine mRNA levels were measured in wound biopsies during the first week of healing...
November 1, 2016: Advances in Wound Care
https://www.readbyqxmd.com/read/27859546/first-in-human-randomised-study-of-bimekizumab-a-humanised-monoclonal-antibody-and-selective-dual-inhibitor-of-il-17a-and-il-17%C3%A2-f-in-mild-psoriasis
#7
S Glatt, E Helmer, B Haier, F Strimenopoulou, G Price, P Vajjah, O A Harari, J Lambert, S Shaw
AIMS: Assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab, (formerly UCB4940), a novel humanised monoclonal antibody and dual inhibitor of interleukin (IL)-17A and IL-17 F, in subjects with mild plaque psoriasis. METHODS: Randomised, double-blind, first-in-human study of bimekizumab in 39 subjects who received single-dose intravenous (iv) bimekizumab (8-640 mg) or placebo (NCT02529956). RESULTS: Bimekizumab demonstrated dose-proportional linear PK and was tolerated across the dose range assessed...
November 13, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27859256/proinflammatory-effect-of-hmgb1-on-keratinocytes-an-autocrine-mechanism-underlying-psoriasis-development
#8
Weigang Zhang, Sen Guo, Bing Li, Lin Liu, Rui Ge, Tianyu Cao, Huina Wang, Tianwen Gao, Gang Wang, Chunying Li
Psoriasis is an autoimmune skin disease, in which keratinocytes play a crucial pathogenic role. High-mobility group protein B1 (HMGB1) is an inflammatory factor that can be released from keratinocyte nuclei in psoriatic lesions. We aimed to investigate the proinflammatory effect of HMGB1 on keratinocytes and the contribution of HMGB1 to psoriasis development. Normal human keratinocytes were treated with recombinant human HMGB1, and the production of inflammatory factors and the intermediary signaling pathways were examined...
November 14, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27857980/cutaneous-expression-of-a-disintegrin-like-and-metalloprotease-domain-containing-thrombospondin-type-1-motif-like-5-adamtsl5-in-psoriasis-goes-beyond-melanocytes
#9
Kathleen M Bonifacio, Norma Kunjravia, James G Krueger, Judilyn Fuentes-Duculan
A Disintegrin-like and Metalloprotease domain containing Thrombospondin type 1 motif-like 5 (ADAMTSL5) is a melanocyte-derived protein that has recently been implicated as an activating antigen for IL-17-producing T cells in psoriasis. There is a potential disconnect between the basal location of the melanocytes in the epidermis and the fact that T-cell infiltrates are seen mostly scattered in the epidermis with very large infiltrates in the dermis. Thus, we hypothesized that ADAMTSL5 may be expressed in other cells aside from melanocytes in skin...
October 2016: Journal of Pigmentary Disorders
https://www.readbyqxmd.com/read/27856660/effect-of-il-17-receptor-a-blockade-with-brodalumab-in-inflammatory-diseases
#10
REVIEW
Ajay Nirula, Jon Nilsen, Paul Klekotka, Greg Kricorian, Ngozi Erondu, Jennifer E Towne, Chris B Russell, David A Martin, Alison L Budelsky
IL-17 cytokines are expressed by a variety of cells and mediate host defence against extracellular pathogens. IL-17 is upregulated at sites of inflammation and can synergize with other cytokines, such as TNF-α, to amplify the inflammatory response. Activation of these signalling pathways has been hypothesized to contribute to the underlying pathogenesis of several inflammatory diseases, including psoriasis, RA, PsA and asthma. Thus the IL-17 signalling pathway is an attractive target for the development of therapeutic agents to modulate aberrant inflammatory responses...
December 2016: Rheumatology
https://www.readbyqxmd.com/read/27836567/management-of-psoriatic-arthritis-early-diagnosis-monitoring-of-disease-severity-and-cutting-edge-therapies
#11
REVIEW
Siba P Raychaudhuri, Reason Wilken, Andrea C Sukhov, Smriti K Raychaudhuri, Emanual Maverakis
Psoriatic arthritis (PsA) is a heterogeneous disease that can involve a variety of distinct anatomical sites including a patient's peripheral and axial joints, entheses, skin and nails. Appropriate management of PsA requires early diagnosis, monitoring of disease activity, and utilization of cutting edge therapies. To accomplish the former there are a variety of PsA-specific tools available to screen, diagnose, and assess patients. This review will outline the recently developed PsA screening tools, including the Toronto Psoriatic Arthritis Screening Questionnaire (TOPAS), the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Psoriasis and Arthritis Screening Questionnaire (PASQ)...
November 8, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27825174/a-review-of-ixekizumab-an-anti-interleukin-17a-monoclonal-antibody-for-moderate-to-severe-plaque-psoriasis
#12
A J Peranteau, A E Turkeltaub, Y Tong, Z Nawas, S K Tyring
Psoriasis is a multifactorial chronic skin disease that can have significant detrimental effects on patients' physical, mental, antibodypsychosocial wellbeing. Patients often suffer from a decreased quality of life along with numerous comorbidities. Recent advances in our understanding of the innate and adaptive immune systems have led to the identification of interleukin (IL)-17 as a key pro-inflammatory mediator in psoriasis. This knowledge has in turn led to the development of newer biologic agents that have been shown to be more effective than traditional therapies...
November 2016: Skin Therapy Letter
https://www.readbyqxmd.com/read/27824222/association-between-endocrinological-immunological-and-psychosocial-variables-in-psoriasis-patients
#13
Özlem Bilgiç, Ayhan Bilgiç, Abdullah Sivrikaya, Yavuz Selvi, Ali Ünlü, Hilmi C Altinyazar
BACKGROUND: There is limited data concerning the relationship between psychosocial problems of psoriasis patients and the function of their hypothalamic-pituitary-adrenal (HPA) axis and immunologic markers. This study aimed to determine serum levels of basal cortisol and adrenocorticotropic hormone (ACTH) and circulating levels of various cytokines and chemokines and their association with psychological measures in psoriasis patients. METHODS: Serum concentrations of endocrinological and immunological variables were quantified, and psychiatric questionnaires were completed...
December 2016: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/27810232/potential-role-of-il-17-producing-cd4-cd8-double-negative-%C3%AE-%C3%AE-t-cells-in-psoriatic-skin-inflammation-in-a-tpa-induced-stat3c-transgenic-mouse-model
#14
Azumi Ueyama, Chihiro Imura, Yasuyuki Fusamae, Kenichiro Tsujii, Yoko Furue, Miwa Aoki, Minoru Suzuki, Tomohiko Okuda, Itsuki Oshima, Kiyoshi Yasui, Michitaka Shichijo, Mina Yamamoto
BACKGROUND: Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders and is accompanied by erythematous scaly plaques. There is growing evidence that the IL-23/Th17 axis plays a critical role in development of the disease. It was recently shown that in addition to CD4(+) Th17 cells, various IL-17-producing cell subsets such as CD8(+) Tc17 cells, dermal γδ T cells, and innate lymphoid cells are also involved in the development of psoriatic inflammation in humans...
October 19, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27785085/treatment-challenges-in-the-management-of-moderate-to-severe-plaque-psoriasis-role-of-secukinumab
#15
REVIEW
Mona Malakouti, Sharon E Jacob, Nancy J Anderson
Psoriasis is a chronic inflammatory skin disease that has a negative impact on psychosocial well-being and cardiometabolic health. Treatment options for moderate-to-severe psoriasis have expanded with the development of interleukin-17 (IL-17) inhibitors, the first of which is now available - secukinumab. Secukinumab is a fully human monoclonal immunoglobulin G1 κ antibody that selectively inhibits the ligand IL-17A. In head-to-head studies, it is more effective than etanercept and ustekinumab, particularly in achieving Psoriasis Area and Severity Index (PASI) 90/100 and achieving PASI 50/75 as early as week 4...
2016: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/27777066/psoralen-loaded-liposomal-nanocarriers-for-improved-skin-penetration-and-efficacy-of-topical-puva-in-psoriasis
#16
Sindhu Doppalapudi, Anjali Jain, Dhiraj Kumar Chopra, Wahid Khan
Psoralen in combination with ultraviolet A radiation (PUVA) is an FDA recommended therapy for clinical application in the management of severe recalcitrant psoriasis. Psoralen acts by intercalation of DNA and upon exposure to UV-A, it forms monoadducts which inturn induce apoptosis. Poor skin deposition, weak percutaneous permeability of psoralen and adverse effects of severe burning, blisters, pigmentation associated with conventional topical psoralen vehicles hinders the therapeutic efficacy and safety of topical PUVA...
October 21, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27774581/a-preliminary-study-of-new-single-polymorphisms-in-th17-pathway-for-psoriasis-in-the-korean-population
#17
Soo Young Kim, Min Seok Hur, Byung Gon Choi, Min Jung Kim, Yang Won Lee, Yong Beom Choe, Kyu Joong Ahn
Psoriasis is a polygenic and multifactorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin 17A (IL-17A), interleukin 17 receptor (IL-17R), and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis...
October 24, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27774460/activated-circulating-t-follicular-helper-cells-are-associated-with-disease-severity-in-patients-with-psoriasis
#18
Ying Wang, Lili Wang, Haoyu Yang, Weichang Yuan, Jingyi Ren, Yanping Bai
Circulating T follicular helper (cTfh) cells are known to be involved in numerous immune-mediated diseases, but their pathological role in psoriasis is less fully investigated. Herein, we aimed to identify whether cTfh cells contributed to the pathogenesis of psoriasis. The frequency and function of cTfh cells were compared between patients with psoriasis vulgaris and healthy controls, and the infiltration of Tfh cells was detected between lesional and nonlesional skin tissues of psoriasis patients. Moreover, the dynamic change of cTfh cells before and after acitretin treatment was evaluated...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27773660/psoriatic-inflammation-causes-hepatic-inflammation-with-concomitant-dysregulation-in-hepatic-metabolism-via-il-17a-il-17-receptor-signaling-in-a-murine-model
#19
Naif O Al-Harbi, Ahmed Nadeem, Mohammed M Al-Harbi, Khairy M A Zoheir, Mushtaq A Ansari, Ahmed M El-Sherbeeny, Khalid M Alanazi, Moureq R Alotaibi, Sheikh F Ahmad
Psoriatic inflammation has been shown to be associated with cardiovascular dysfunction and systemic inflammation. Recently, psoriasis has also been linked to hepatic disorders, however underlying mechanism connecting the two are unknown. IL-17A being a central pro-inflammatory cytokine in the pathogenesis of psoriasis may be involved in hepatic inflammation through its receptor and downward signaling; however so far no study has investigated IL-17A related signaling in the liver during psoriasis in a murine model...
October 18, 2016: Immunobiology
https://www.readbyqxmd.com/read/27772545/in-the-red-deficits-in-immune-regulation-underlie-psoriasis-severity
#20
Andrew Johnston
IL-17-driven pathways are active in the skin of patients with psoriasis. Kim et al. examined lesions from mild and moderate to severe psoriasis and found that differences in cutaneous disease severity may be the outcome of lapses in immunoregulatory mechanisms; because as much, if not more, T helper type 17-induced inflammation was seen in mild psoriasis, these patients may also benefit from anti-IL-17-targeted biologics.
November 2016: Journal of Investigative Dermatology
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