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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/28791896/biologics-that-inhibit-the-th17-pathway-and-related-cytokines-to-treat-inflammatory-disorders
#1
Anna Balato, Emanuele Scala, Nicola Balato, Giuseppina Caiazzo, Roberta Di Caprio, Giuseppe Monfrecola, Annunziata Raimondo, Serena Lembo, Fabio Ayala
Advances in the understanding of TNF-α and IL-17 synergistic functions have recently led to the concept that patients who do not respond or who respond inadequately to TNF-α inhibitors may have IL-17-driven diseases, opening up the way for a new class of therapeutic development: Th17-inhibitors. Areas covered: In this review, the authors discuss the central role that the IL-23/Th17 axis plays in the pathogenesis of several inflammatory diseases, such as psoriasis, highlighting its position as a relevant therapeutic target...
August 9, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28790368/signs-of-innate-immune-activation-and-premature-immunosenescence-in-psoriasis-patients
#2
Liisi Šahmatova, Elena Sügis, Marina Šunina, Helen Hermann, Ele Prans, Maire Pihlap, Kristi Abram, Ana Rebane, Hedi Peterson, Pärt Peterson, Külli Kingo, Kai Kisand
Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28780985/9-19-cycloartenol-glycoside-g3-from-cimicifuga-simplex-regulates-immune-responses-by-modulating-th17-treg-ratio
#3
Yang Su, Lun Wu, Guangrui Mu, Qiuhong Wang, Bingyou Yang, Genhong Cheng, Haixue Kuang
Cimicifuga simplex is a medicinal herb which has a wide range of biological activities. We isolated seven 9,19-cycloartenol glycosides from the roots of C. simplex, and among the glycosides, G3 exhibited the strongest inhibitory effect on immune responses, including suppressing the differentiation of CD(4+) T cells and directly suppressing the cytokine-induced JAK/STAT signaling pathways. In the IL-23-induced mouse ear model of skin disease, G3 repressed disease development by inhibiting the expression of pro-inflammatory mediators in murine ear skin...
July 27, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28780731/unmet-needs-in-the-field-of-psoriasis-pathogenesis-and-treatment
#4
REVIEW
Wolf-Henning Boehncke, Nicolo Costantino Brembilla
In times of targeted therapies, innovative therapeutics become tools to further unravel the pathogenesis of the treated disease, thus influencing current pathogenetic concepts. Based on such paradigm shifts, the next generation of novel therapeutic targets might be identified. Psoriasis is a good example for the resulting most fruitful dialog between clinical and fundamental research. As a result of this, the key role of Th17 lymphocytes, some of their effector molecules, as well as mediators contributing to their maturation have been identified, many of these being targeted by some of the most effective drugs currently available to treat psoriasis...
August 6, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28770513/selective-interleukin-23-p19-inhibition-another-game-changer-in-psoriasis-focus-on-risankizumab
#5
Tiago Torres
The history of psoriasis treatment has been marked by several milestones. Corticosteroids, cyclosporine, tumor necrosis factor alpha (TNF-α) inhibitors and, more recently, interleukin (IL)-17A inhibitors have revolutionized the treatment of psoriasis, each in its own way and time. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis and selective IL-23p19 inhibition may bring several advantages with respect to IL-12/23p40 inhibition, or distal blockade of IL-17A or its receptor...
August 2, 2017: Drugs
https://www.readbyqxmd.com/read/28768901/essential-role-for-ccr6-in-certain-inflammatory-diseases-demonstrated-using-specific-antagonist-and-knockin-mice
#6
Remy Robert, Caroline Ang, Guizhi Sun, Laurent Juglair, Ee X Lim, Linda J Mason, Natalie L Payne, Claude Ca Bernard, Charles R Mackay
The chemokine receptor CCR6 marks subsets of T cells and innate lymphoid cells that produce IL-17 and IL-22, and as such may play a role in the recruitment of these cells to certain inflammatory sites. However, the precise role of CCR6 has been controversial, in part because no effective monoclonal antibody (mAb) inhibitors against this receptor exist for use in mouse models of inflammation. We circumvented this problem using transgenic mice expressing human CCR6 (hCCR6) under control of its native promoter (hCCR6-Tg/mCCR6-/-)...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28765121/novel-therapies-for-immune-mediated-inflammatory-diseases-what-can-we-learn-from-their-use-in-rheumatoid-arthritis-spondyloarthritis-systemic-lupus-erythematosus-psoriasis-crohn-s-disease-and-ulcerative-colitis
#7
REVIEW
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
August 1, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28750567/impact-of-pharmacogenomics-upon-the-therapeutic-response-to-etanercept-in-psoriasis-and-psoriatic-arthritis
#8
Giuseppe Murdaca, Simone Negrini, Ottavia Magnani, Elena Penza, Marco Pellecchio, Francesco Puppo
TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a decoy receptor" for TNF-α and it is composed of two p75 TNF-α receptors fused to human IgG1. Areas covered: We discuss the potential role of pharmacogenetics in predicting the response to etanercept in patients with Ps and PsA. Expert opinion: Pharmacogenetics represents the new frontier for the discovery of potential genetic markers of biological response to TNF-α inhibitors...
July 28, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28744098/spotlight-on-brodalumab-in-the-treatment-of-moderate-to-severe-plaque-psoriasis-design-development-and-potential-place-in-therapy
#9
REVIEW
Michael Roman, Melvin W Chiu
Brodalumab is a novel fully human immunoglobulin G2 monoclonal antibody that antagonizes the interleukin (IL)-17 pathway by binding with high affinity to human IL-17RA. The role of IL-17A in the pathogenesis of psoriasis, as well as the remarkable effectiveness of IL-17 inhibitors in the treatment of moderate-to-severe plaque psoriasis, is well established. The mechanism of action of brodalumab is unique in that it inhibits the IL-17 receptor compared to the two other currently FDA-approved IL-17 inhibitors, secukinumab and ixekizumab, which inhibit the IL-17A molecule itself...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28738533/mir-200a-expression-in-cd4-t-cells-correlates-with-the-expression-of-th17-treg-cells-and-relevant-cytokines-in-psoriasis-vulgaris-a-case-control-study
#10
Xiao-Yan Wang, Xing-Yu Chen, Jun Li, Hong-Ying Zhang, Juan Liu, Le-Dong Sun
The main aim of this study is to investigate the underlying relationship shared between microRNA-200a (miR-200a) and its link to concentrations of Th17 and Treg cells, mRNA expressions of their specific transcription factors retinoic acid-related orphan receptor γt (RORγt) and head box protein 3 (FOXP3) and relevant cytokines in patients with psoriasis vulgaris (PV). A total of 189 patients previously diagnosed with PV were selected as the experimental group, whilst 109 healthy individuals as the control group...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28736282/imiquimod-induced-psoriasis-like-inflammation-in-differentiated-human-keratinocytes-its-evaluation-using-curcumin
#11
Sandeep R Varma, Thiyagarajan O Sivaprakasam, Abheepsa Mishra, Sunil Prabhu, Rafiq M, Rangesh P
Psoriasis is considered to be a systemic disease of immune dysfunction. It is still unclear what triggers the inflammatory cascade associated with psoriasis but recent evidences suggest the vital role of IL-23/IL-17A cytokine axis in etiology of psoriasis. Several studies have been conducted in psoriatic-like animal models but ethical issues and complexity surrounding it halts the screening of new anti-psoriatic drug candidates. Hence, in this study, we developed a new in-vitro model for psoriasis using imiquimod (IMQ) induced differentiated HaCaT cells which could be used for screening of new anti-psoriatic drug candidates...
July 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28733990/dimethyl-fumarate-modulates-neutrophil-extracellular-trap-formation-in-a-glutathione-and-superoxide-dependent-manner
#12
J H O Hoffmann, K Schaekel, D Hartl, A H Enk, E N Hadaschik
BACKGROUND: Neutrophil (polymorphonuclear) granulocytes (PMN) were shown to contribute to the pathogenesis of psoriasis by releasing IL-17 and LL-37/ DNA complexes via neutrophil extracellular traps (NET), webs of chromatin strands decorated with antimicrobial peptides, in psoriatic skin. Fumaderm(®) , a fumaric acid ester (FAE) formulation consisting of different FAE salts has been successfully used to treat psoriasis for decades. Most recently, FAE treatment was reported to inhibit NET formation in murine epidermolysis bullosa acquisita...
July 22, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28732152/secukinumab-in-the-treatment-of-psoriasis-and-psoriatic-arthritis-a-review-of-the-literature
#13
M Abrouk, J Gandy, M Nakamura, K Lee, M Brodsky, R Singh, H Zhu, B Farahnik, T Bhutani, J Koo
While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis...
July 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28730954/evaluation-of-in-vitro-anti-psoriatic-activity-of-a-novel-polyherbal-formulation-by-multiparametric-analysis
#14
Nadav Shraibom, Alka Madaan, Vidushi Joshi, Ritu Verma, Anika Chaudhary, Gautam Mishra, Anshumali Awasthi, Anu Taneja Singh, Manu Jaggi
The beneficial role of traditional herbal medicines in the treatment of inflammatory skin disorders has been widely reported. Psoriasis is characterized by uncontrolled hyper-proliferation of keratinocytes, disturbed apoptosis, over-secretion of inflammatory cytokines and angiogenic factors. We have developed a novel aqueous polyherbal formulation (SIRB-001) consisting of 3 herbs; Rheum palmatum L., Rehmannia glutinosa Libosch and Lonicera Japonica in the ratio 1:1:3. SIRB-001 has demonstrated efficacious effects in psoriasis patients...
July 20, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28718898/exposure-to-biologic-therapies-during-conception-and-pregnancy-a-systematic-review
#15
E M Pottinger, R T Woolf, L S Exton, A D Burden, C Nelson-Piercy, C H Smith
Biologic therapies are effective treatments for psoriasis and are often used in women of childbearing age. To evaluate the safety of biologic therapy in conception and/or pregnancy, we have performed a systematic review of Pubmed, MEDLINE, EMBASE and Cochrane databases for multivariable adjusted studies of women exposed to biologic therapy relevant to the treatment of psoriasis during conception and/or pregnancy. We identified four population-based cohort studies involving 1300 women exposed to TNF-α inhibitors (TNFi) 3 months prior to or during the first 3 months of pregnancy...
July 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28697222/injection-site-reactions-to-biologic-agents-used-in-psoriasis-and-psoriatic-arthritis
#16
Meagan-Helen Henderson Berg, Daniel Carrasco
<p>Psoriasis is a chronic inflammatory cutaneous disease that affects 2-3% of the general population. Up to 30% of patients with psoriasis also develop psoriatic arthritis, a chronic inflammatory and progressive arthritis. Although their precise pathogeneses remain unclear, psoriasis and psoriatic arthritis involve altered expression of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-12, IL-17, IL-22, and IL-23. The development of biologic agents that target these cytokines has greatly improved the treatment of psoriatic disease...
July 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28677206/imiquimod-applied-interleukin-10-deficient-mice-better-reflects-severe-and-persistent-psoriasis-with-systemic-inflammatory-state
#17
Seon-Pil Jin, Seong-Joon Koh, Da-Ae Yu, Min-Woo Kim, Hee Tae Yun, Dong Hun Lee, Hyun-Sun Yoon, Soyun Cho, Hyun-Sun Park
Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison to previous models. IL-10 deficient and wild type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15...
July 4, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28672038/t-cell-activation-and-differentiation-is-modulated-by-a-cd6-domain-1-antibody-itolizumab
#18
Usha Bughani, Arindam Saha, Anshu Kuriakose, Reshmi Nair, Ravindra B Sadashivarao, Rasika Venkataraman, Swati Patel, Anuja Tushar Deshchougule, Satish Kumar S, Enrique Montero, Harish V Pai, Dinesh V Palanivelu, Ramakrishnan Melarkode, Pradip Nair
CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1) specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17) have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28667777/review-of-phase-iii-trial-data-on-il-23-inhibitors-tildrakizumab-and-guselkumab-for-psoriasis
#19
REVIEW
M Amin, K Darji, D J No, J J Wu
BACKGROUND: The development of monoclonal antibodies targeting IL-12 and IL-23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL-23 alone plays a role in the pathogenesis of psoriasis. OBJECTIVE: The objective was to review the phase III clinical trial data for the anti-IL-23 agents in order to evaluate the safety and efficacy profile of each agent. METHODS: We reviewed the results of the phase III clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab...
July 1, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28667056/endogenous-endophthalmitis-and-osteomyelitis-associated-with-interleukin-17-inhibitor-treatment-for-psoriasis-in-a-patient-with-diabetes
#20
Christine E Martinez, John B Allen, Frederick H Davidorf, Colleen M Cebulla
A 64-year-old man with type 2 diabetes mellitus and plaque psoriasis presented to the emergency room with 3 days of progressive right eye pain and decreased vision. After extensive workup and multidisciplinary team effort, the patient was diagnosed with and treated for unilateral endogenous methicillin-sensitive Staphylococcus aureus endophthalmitis, bacteraemia and osteomyelitis of the foot. The patient had been started on the interleukin 17 (IL-17) inhibitor secukinumab for his treatment-resistant plaque psoriasis 4 weeks prior to presentation...
June 29, 2017: BMJ Case Reports
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