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IL-17 and psoriasis

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https://www.readbyqxmd.com/read/28439340/the-role-of-il-17-in-the-pathogenesis-and-treatment-of-psoriasis
#1
REVIEW
Joshua A Zeichner, April Armstrong
No abstract text is available yet for this article.
June 2016: Journal of Clinical and Aesthetic Dermatology
https://www.readbyqxmd.com/read/28422002/treatment-of-psoriasis-with-ustekinumab-improved-skin-tightening-in-systemic-sclerosis
#2
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/28390815/act1-a-psoriasis-susceptibility-gene-playing-its-part-in-keratinocytes
#3
Ryan P Hobbs, Susan H Smith, Spiro Getsios
Unchecked inflammation, impaired keratinocyte differentiation, and heightened host defense responses typify psoriasis. Lambert et al. make clever use of psoriasis patient genetics and whole transcriptome RNA-Seq analysis to implicate Act1 in these seemingly variegated processes by keeping IL-17 receptor signaling in check while supporting differentiation and limiting innate immune responses in human keratinocytes.
April 5, 2017: Journal of Investigative Dermatology
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
#4
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/28386999/psoriatic-cutaneous-inflammation-promotes-human-monocyte-differentiation-into-active-osteoclasts-facilitating-bone-damage
#5
Annunziata Raimondo, Serena Lembo, Roberta Di Caprio, Giovanna Donnarumma, Giuseppe Monfrecola, Nicola Balato, Fabio Ayala, Anna Balato
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy that can be associated with focal bone erosions. Psoriasis usually precedes the psoriatic arthritis onset by an average of 10 years, but this relation is not yet fully elucidated. Pro-inflammatory cytokines, such as IL-33, OPN, IL-17 and TNF-α are involved in both psoriasis and PsA pathogenesis as well as in bone homeostasis. In this study, we have demonstrated that IL-33, OPN, IL-17 and TNF-α induced the release of a wide range of pro-osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts...
April 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28370441/adverse-skin-reaction-to-secukinumab
#6
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/28366479/biologic-therapy-in-the-treatment-of-chronic-skin-disorders
#7
REVIEW
James M Fernandez, Anthony P Fernandez, David M Lang
Understanding of the immunologic pathways involved in the pathogenesis of skin-related diseases is constantly advancing. Several biologic agents play important therapeutic roles for management of patients with chronic urticaria, atopic dermatitis, and psoriasis, particularly omalizumab for antihistamine-resistant chronic urticaria, interleukin (IL)-1 inhibitors for cryopyrin-associated periodic syndrome and Schnitzler syndrome, dupilumab for recalcitrant atopic dermatitis, and IL-17 inhibitors for psoriasis...
May 2017: Immunology and Allergy Clinics of North America
https://www.readbyqxmd.com/read/28352182/role-of-il-17-in-plaque-psoriasis-therapeutic-potential-of-ixekizumab
#8
REVIEW
Tessa L Hanley, Zenas Zn Yiu
Developments in the understanding of the immunopathogenesis of psoriasis have identified interleukin (IL)-17 as the key proinflammatory cytokine in the pathogenesis of plaque psoriasis, with the consequent development of drugs that target this cytokine or associated receptors. Ixekizumab is a subcutaneously administered humanized monoclonal antibody, which acts to neutralize IL-17A. This article reviews the role of IL-17 in the pathogenesis of psoriasis, the biological and pharmacokinetics of ixekizumab and the safety profile and the clinical efficacy of ixekizumab in Phase III clinical trials...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28319618/new-biologics-in-psoriasis-an-update-on-il-23-and-il-17-inhibitors
#9
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/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#10
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28301691/interleukin-32-is-highly-expressed-in-lesions-of-hidradenitis-suppurativa
#11
R Thomi, D Yerly, N Yawalkar, D Simon, C Schlapbach, R E Hunger
BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Its immunopathogenic mechanisms are still poorly understood. Previous studies could demonstrate that the pro-inflammatory cytokine Interleukin-32 (IL-32) is implicated in the pathogenesis of other inflammatory diseases. OBJECTIVES: The aim of our study was to investigate the tissue expression and systemic levels of IL-32 as well as its cellular sources in HS patients in comparison to healthy donors and to patients suffering from two other inflammatory skin diseases: psoriasis (PS) and atopic dermatitis (AD)...
March 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28299442/interleukin-il-18-cooperatively-with-il-23-induces-prominent-inflammation-and-enhances-psoriasis-like-epidermal-hyperplasia
#12
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/28296664/histomorphology-and-immunophenotype-of-eczematous-skin-lesions-revisited-skin-biopsies-are-not-reliable-in-differentiating-allergic-contact-dermatitis-irritant-contact-dermatitis-and-atopic-dermatitis
#13
Verena G Frings, Almut Böer-Auer, Kristine Breuer
Lesions of allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), and atopic dermatitis (AD) share similar clinical features and thus, their diagnosis can be challenging. The aim of this study was to reassess histopathology and immunophenotyping properties to distinguish between ACD, ICD, and AD. Charts of patients with eczema, who had undergone complete routine diagnostic workup (skin biopsies, patch tests, skin prick tests, and respectively or serum IgE levels), were reviewed. Thirty-five skin biopsy specimens of 28 patients (mean age 64 ± 15 years; ♀ = 13 ♂ = 15) with clear diagnosis of ACD (n = 15), ICD (n = 6), or AD (n = 14) were analyzed...
March 10, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28285360/kynurenic-acid-downregulates-il-17-1l-23-axis-in-vitro
#14
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/28280792/inhibition-of-interleukin-17-a-but-not-interleukin-17f-signaling-lowers-blood-pressure-and-reduces-end-organ-inflammation-in-angiotensin-ii-induced-hypertension
#15
Mohamed A Saleh, Allison E Norlander, Meena S Madhur
OBJECTIVES: To characterize the T cell subsets producing interleukin 17 (IL-17) isoforms A and F in hypertensive kidneys and vessels and determine whether inhibition of IL-17 signaling lowers blood pressure and end-organ damage in a mouse model of hypertension. BACKGROUND: T cell derived cytokines play a central role in the pathophysiology of hypertension and contribute to end-organ dysfunction. We previously showed that mice genetically deficient in IL-17A exhibited blunted hypertension and reduced renal and vascular dysfunction in response to angiotensin II (Ang II) infusion...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28274739/dual-role-of-act1-in-keratinocyte-differentiation-and-host-defense-traf3ip2-silencing-alters-keratinocyte-differentiation-while-inhibiting-il-17-responses
#16
Sylviane Lambert, William R Swindell, Lam C Tsoi, Stefan W Stoll, James T Elder
TRAF3IP2 is a candidate psoriasis susceptibility gene encoding Act1, an adaptor protein with ubiquitin ligase activity that couples the IL-17 receptor to downstream signaling pathways. We investigated the role of Act1 in keratinocyte responses to IL-17 using a tetracycline inducible shRNA targeting TRAF3IP2. Tet exposure for seven days effectively silenced TRAF3IP2 mRNA and Act1 protein, resulting in 761 genes with significant changes in expression (495 down, 266 up, >1.5-fold, p<0.05). Gene Ontology analysis revealed that genes affected by TRAF3IP2 silencing are involved in epidermal differentiation, with early differentiation genes (KRT1, KRT10, DSC1, DSG1) being downregulated and late differentiation genes (SPRR2, SPRR3, LCE3) being upregulated...
March 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28270233/mechanistic-rationales-for-targeting-interleukin-17a-in-spondyloarthritis
#17
REVIEW
Siba P Raychaudhuri, Smriti K Raychaudhuri
The term spondyloarthritis (SpA) is used to describe a group of inflammatory autoimmune diseases, including ankylosing spondylitis and psoriatic arthritis, with common genetic risk factors and clinical features. SpA is clinically distinct from rheumatoid arthritis and typically affects the spine, sacroiliac joints, entheses, and, less commonly, peripheral joints. Although the pathogenesis of SpA is not fully understood, recent findings have identified the interleukin (IL)-17 pathway as a key mediator of disease pathogenesis...
March 8, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28243466/update-on-interleukin-17-a-role-in-the-pathogenesis-of-inflammatory-arthritis-and-implication-for-clinical-practice
#18
REVIEW
Pierre Miossec
Interleukin-17 (IL-17A) is a cytokine critical for the acute defence against extracellular bacterial and fungal infections. Excess production during chronic inflammation has been associated with many inflammatory and autoimmune disorders. The present review describes the key molecules of the IL-17 pathway, which are or could be targeted for treatment. Since targeting of IL-17A may affect defence mechanisms, the pathogenesis of such possible adverse events is analysed. Then the contributions of IL-17 to bone changes in various forms of arthritis are discussed...
2017: RMD Open
https://www.readbyqxmd.com/read/28239238/cytokine-imbalance-as-a-common-mechanism-in-both-psoriasis-and-rheumatoid-arthritis
#19
Yong Tan, Qiu Qi, Cheng Lu, Xuyan Niu, Yanping Bai, Chunyan Jiang, Yang Wang, Youwen Zhou, Aiping Lu, Cheng Xiao
Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28239073/effects-of-topical-application-of-betamethasone-on-imiquimod-induced-psoriasis-like-skin-inflammation-in-mice
#20
Hiroki Mori, Kojo Arita, Takayuki Yamaguchi, Midori Hirai, Yoichi Kurebayashi
Psoriasis is a chronic inflammatory skin disease mediated by dysregulated auto-reactive immune system. In this study, in order to confirm and further extend the pharmacological basis of topical steroids in psoriasis therapy, we investigated the effect of betamethasone ointment on imiquimod (IMQ)-induced skin inflammation in mice. In BALB/c mice, topical IMQ at the dose of 250 µg each on both sides of the ear induced marked psoriasis-like skin inflammation within 5 days. The same dose of IMQ produced only slight to moderate skin inflammation even on Day 7 in CB-17 scid mice...
September 9, 2016: Kobe Journal of Medical Sciences
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