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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/28645307/aberrant-intestinal-microbiota-due-to-il-1-receptor-antagonist-deficiency-promotes-il-17-and-tlr4-dependent-arthritis
#1
Rebecca Rogier, Thomas H A Ederveen, Jos Boekhorst, Harm Wopereis, Jose U Scher, Julia Manasson, Sanne J C M Frambach, Jan Knol, Johan Garssen, Peter M van der Kraan, Marije I Koenders, Wim B van den Berg, Sacha A F T van Hijum, Shahla Abdollahi-Roodsaz
BACKGROUND: Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn (-/-) mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn (-/-) mice...
June 23, 2017: Microbiome
https://www.readbyqxmd.com/read/28633806/il-17-for-therapy
#2
REVIEW
Florian C Kurschus, Sonja Moos
The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis...
June 15, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28624119/skin-infiltrating-interleukin-22-producing-t-cells-differentiate-pediatric-psoriasis-from-adult-psoriasis
#3
Kelly M Cordoro, Maria Hitraya-Low, Keyon Taravati, Priscila Munoz Sandoval, Esther Kim, Jeffrey Sugarman, Mariela L Pauli, Wilson Liao, Michael D Rosenblum
BACKGROUND: Evidence from adult psoriasis studies implicates an imbalance between regulatory and effector T cells, particularly TH-17-producing T cells, in the pathogenesis of psoriasis. Little is known about the immunopathology of psoriasis in children. OBJECTIVE: We sought to functionally characterize the inflammatory cell profiles of psoriatic plaques from pediatric patients and compare them with healthy, age-matched controls and adult psoriasis patients. METHODS: Skin samples from pediatric psoriasis patients and healthy controls were analyzed by multiparameter flow cytometry to determine the dominant immune cell subsets present and cytokines produced...
June 14, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28620097/interleukin-17-family-cytokines-signaling-mechanisms-biological-activities-and-therapeutic-implications
#4
Leticia Monin, Sarah L Gaffen
The cytokines of the interleukin 17 (IL-17) family play a central role in the control of infections, especially extracellular fungi. Conversely, if unrestrained, these inflammatory cytokines contribute to the pathology of numerous autoimmune and chronic inflammatory conditions. Recent advances have led to the approval of IL-17A-blocking biologics for the treatment of moderate to severe plaque psoriasis, but much remains to be understood about the biological functions, regulation, and signaling pathways downstream of these factors...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28617942/withasteroid-b-from-d-metel-l-regulates-immune-responses-by-modulating-the-jak-stat-pathway-and-the-il-17-ror%C3%AE-t-il-10-foxp3-ratio
#5
Yang Su, Qiuhong Wang, Bingyou Yang, Lun Wu, Genhong Cheng, Haixue Kuang
Datura metel L. is a medicinal herb that contains withasteroids and has a wide range of biological activities. We isolated 7 withasteroids from the flowers of D. metel L(1) . and examined their ability to inhibit immune responses in vitro and in vivo. Among the withasteroids, B2(2) exhibited the strongest inhibitory effect on immune responses comparing B2 with other isolated compounds from D. metel L., including suppressing the differentiation of CD4(+3) T cells by inhibiting the expression and production of T cell lineage-specific master regulators and cytokines and directly suppressing the cytokine-induced JAK/STAT(4) signaling pathways...
June 15, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28602508/cyr61-ccn1-induces-ccl20-production-by-keratinocyte-via-activating-p38-and-jnk-ap-1-pathway-in-psoriasis
#6
Huidan Li, Haichuan Li, Rongfen Huo, Pinru Wu, Zhengyu Shen, Hui Xu, Baihua Shen, Ningli Li
BACKGROUND: Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) has recently been implicated in psoriasis pathogenesis by promoting keratinocyte activation. However, the mechanisms by which CCN1 enhances cutaneous inflammation are not fully understood. OBJECTIVE: In this study, we investigated the role of CCN1 on the expression of CCL20 in human keratinocyte. METHODS AND RESULTS: By double-label immunofluorescence staining, we first identified that the expression of CCN1 colocalized well with CCL20 production in the epidermis of psoriasis skin lesion...
June 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28597992/systemic-ala-pdt-effectively-blocks-the-development-of-psoriasis-like-lesions-and-alleviates-leucocyte-infiltration-in-the-k14-vegf-transgenic-mouse
#7
T Chen, L-W Zhang, L-X Fu, Y-B Wu, X-Y Liu, Z-P Guo
BACKGROUND: Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders. In spite of significant advances in the treatment of psoriasis, more effective and safer therapeutic strategies are still needed. Photodynamic therapy (PDT) is a method of light treatment that is being used increasingly in the treatment of dermatological diseases. AIM: To evaluate the therapeutic effects of systemic 5-aminolaevulinic acid (ALA)-PDT on psoriasis and to explore its potential mechanism of action...
June 9, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28592369/preliminary-study-of-histamine-h4-receptor-expressed-on-human-cd4-t-cells-and-its-immunomodulatory-potency-in-the-il-17-pathway-of-psoriasis
#8
Song Hee Han, Min Seok Hur, Min Jung Kim, Bo Mi Kim, Kyoung Woon Kim, Hae Rim Kim, Yong Beom Choe, Kyu Joong Ahn, Yang Won Lee
BACKGROUND: Previous studies have shown the expression of histamine H4 receptor (H4R) on CD4(+) T cells, especially human CD4(+) Th2-polarized T cells. OBJECTIVE: This study aimed to investigate the role of H4R on these effector T cells in psoriasis. METHODS: We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4(+) T cells...
May 29, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28585707/early-relapse-of-psoriasis-after-stopping-brodalumab-a-retrospective-cohort-study-in-77-patients
#9
M Masson Regnault, M-P Konstantinou, A Khemis, Y Poulin, M Bourcier, F Amelot, C Bulaï Livideanu, C Paul
BACKGROUND: Biological agents targeting IL-17 are very effective for clearing moderate to severe psoriasis. There is limited information regarding the frequency and pattern of psoriasis relapse upon treatment cessation. OBJECTIVE: To investigate the pattern of psoriasis recurrence in patients who were treated with brodalumab following Amgen's decision to stop the clinical program in June 2015. MATERIALS AND METHODS: Between June 2015 and March 2016, we constructed a retrospective multicenter cohort study including patients who were treated with brodalumab in Amgen's protocols after the abrupt interruption of the drug development program...
June 6, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28579438/imiquimod-induced-apoe-deficient-mice-might-be-a-composite-animal-model-for-the-study-of-psoriasis-and-dyslipideamia-comorbidity
#10
Xinran Xie, Lei Zhang, Yan Lin, Yan Wang, Weihong Liu, Xue Li, Ping Li
BACKGROUND: Psoriasis patients are at increased risk of developing lipid metabolism disturbances. Both psoriasis and dyslipideamia not only closely interact in disease development, but occur as mutual side effects in some medicine treatment. The interactive mechanism of the two diseases is complicated and still unclear. OBJECTIVE: Here, we proposed applying imiquimod on the dorsal skin of ApoE(-/-) mice to establish a composite animal model which formed psoriasiform skin lesions under hyperlipidemic condition...
May 17, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28576737/nrf2-promotes-keratinocyte-proliferation-in-psoriasis-through-up-regulation-of-keratin-6-keratin-16-and-keratin-17
#11
Luting Yang, Xueli Fan, Tingting Cui, Erle Dang, Gang Wang
Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation of epidermis. Although hyperproliferation-associated keratins K6, K16 and K17 are considered to be the hallmarks of psoriasis, the molecular basis underlying the overexpression of these keratins remains unclear. Nuclear factor erythroid-derived 2 related factor 2 (Nrf2) regulates cell proliferation. Therefore, we investigated whether Nrf2 regulates keratinocyte proliferation via promoting expression of K6, K16 and K17 in psoriasis...
May 30, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28554321/phosphodiesterase-4-inhibitors-in-immune-mediated-diseases-mode-of-action-clinical-applications-current-and-future-perspectives
#12
Lazaros I Sakkas, Athanasios Mavropoulos, Dimitrios P Bogdanos
Phosphodiesterase (PDE) 4 is a superfamily of enzymes that catalyze the hydrolysis of cyclic adenosine 3',5'-monophosphate (cAMP), an intracellular second messenger and regulator of a wide array of genes and proteins. Increased levels of intracellular cAMP lead to activation of genes but also to inhibition of nuclear factor-kappa B, involved in pro-inflammatory responses. By increasing cAMP levels, PDE4 inhibitors, such as apremilast, reduced production of pro-inflammatory TNFα, IFNγ, and IL-17 and increased production of anti-inflammatory IL-10 in lipopolysaccharide-stimulated peripheral blood mononuclear cells, and in patients with psoriatic arthritis (PsA)...
May 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28547879/anti-il-17-flared-psoriasis-in-a-patient-on-secukinumab
#13
Claire Noell, Brianna McQuade, Alice Gottlieb, David Rosmarin
No abstract text is available yet for this article.
May 26, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28542874/comparison-of-ixekizumab-with-ustekinumab-in-moderate-to-severe-psoriasis-24-week-results-from-ixora-s-a-phase-3-study
#14
K Reich, A Pinter, J P Lacour, C Ferrandiz, G Micali, L E French, M Lomaga, Y Dutronc, C Henneges, S Wilhelm, S Hartz, C Paul
BACKGROUND: The interleukin (IL)-23/IL-17 axis has been shown critical in the pathogenesis of psoriasis. OBJECTIVES: To present the primary endpoint (Week 12) and safety/efficacy data up to Week 24 from a head-to-head trial (IXORA-S) of the IL-17A inhibitor, ixekizumab (IXE), vs. the IL-12/23 inhibitor ustekinumab (UST). METHODS: Randomised patients received IXE (160-mg starting dose, then 80 mg every two weeks for 12 weeks, then 80 mg every four weeks, N=136) or UST (45 mg/90 mg weight-based dosing per label, N=166)...
May 19, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28535470/pharmacophore-guided-discovery-of-small-molecule-interleukin-15-inhibitors
#15
Barbara Żyżyńska-Granica, Bartosz Trzaskowski, Szymon Niewieczerzał, Sławomir Filipek, Oliwia Zegrocka-Stendel, Małgorzata Dutkiewicz, Piotr Krzeczyński, Magdalena Kowalewska, Katarzyna Koziak
Upregulation of interleukin 15 (IL-15) contributes directly i.a. to the development of inflammatory and autoimmune diseases. Selective blockade of IL-15 aimed to treat rheumatoid arthritis, psoriasis and other IL-15-related disorders has been recognized as an efficient therapeutic method. The aim of the study was to identify small molecules which would interact with IL-15 or its receptor IL-15Rα and inhibit the cytokine's activity. Based on the crystal structure of IL-15Rα·IL-15, we created pharmacophore models to screen the ZINC database of chemical compounds for potential IL-15 and IL-15Rα inhibitors...
May 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28534291/ultra-sensitive-measurement-of-il-17a-and-il-17f-in-psoriasis-patient-serum-and-skin
#16
Catherine Soderstrom, Gabriel Berstein, Weidong Zhang, Hernan Valdez, Lori Fitz, Max Kuhn, Stephanie Fraser
Interleukin 17 is a family of cytokines that play a central role in many autoimmune and inflammatory diseases. IL-17A has been implicated as a key driver of psoriasis, mediating a chronic cycle of T-cell activation, keratinocyte proliferation and angiogenesis. It has been hypothesized that expression of IL-17A and the related cytokine IL-17F could be used as predictive biomarkers for therapeutic response, though they have been difficult to measure locally or in circulation because of their low abundance. We developed ultrasensitive methods for measuring IL-17A and IL-17F in human serum samples and found that serum from psoriasis patients had higher and a broader range of concentrations of both IL-17 proteins compared to healthy volunteers...
May 22, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28532819/il-23-th17-targeted-therapies-in-sapho-syndrome-a-case-series
#17
Daniel Wendling, François Aubin, Frank Verhoeven, Clément Prati
SAPHO syndrome is a rare entity with skin and rheumatologic inflammatory presentation. The treatment is not standardized, and in case of inadequate response to anti inflammatory drugs, the use of anti TNF or anti IL-1 biologic treatments has been reported. The IL-23/Th17 axis may be involved in SAPHO syndrome. We report the results of six courses of IL-23 and IL-17 targeted therapies (3 ustekinumab and 3 secukinumab) in patients with SAPHO syndrome unresponsive to previous treatments (csDMARDs and bDMARDs)...
May 19, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28530223/tweak-mediates-inflammation-in-experimental-atopic-dermatitis-and-psoriasis
#18
Daniel Sidler, Ping Wu, Rana Herro, Meike Claus, Dennis Wolf, Yuko Kawakami, Toshiaki Kawakami, Linda Burkly, Michael Croft
Atopic dermatitis (AD) and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. Here we show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of AD-specific T helper type 2 (Th2) and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in AD, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28521565/interleukin-17-inhibition-role-in-psoriasis-and-inflammatory-bowel-disease
#19
Megan Hohenberger, Leah A Cardwell, Elias Oussedik, Steven R Feldman
INTRODUCTION: Interleukin 17 (IL-17) antagonism provides a highly effective approach for treating psoriasis. Exacerbations of inflammatory bowel disease have been reported in anti-IL-17 psoriasis trials. AIM: To characterize the relationship between IL-17 inhibition and inflammatory bowel disease. METHODS: A review of English-language articles was performed. Search terms included IL-17, psoriasis, inflammatory bowel disease, secukinumab, ixekizumab and brodalumab...
May 31, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28509526/paraoxonases-and-psoriasis-negative-imbalance-of-anti-oxidant-endogenous-mechanisms
#20
Maria Schiattarella, Giuseppina Caiazzo, Roberta DI Caprio, Serena Lembo, Annunziata Raimondo, Fabio Ayala, Nicola Balato, Giuseppe Monfrecola, Giuliana Fortunato, Anna Balato
BACKGROUNG: Numerous reports have shown that psoriasis patients are more exposed to lipoprotein peroxidation and to a decrease in the activity of paraoxonase (PON)1, an anti-oxidant and anti-inflammatory enzyme. Thus, it has been suggested that malfunction of the anti-oxidant system and an increased production of reactive oxygen species drive immune inflammatory events, that result in progressive skin cell damage in patients with psoriasis. The PON protein family, including PON1, PON2 and PON3, is one of the most important endogenous defense mechanisms against oxidative stress...
May 16, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
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