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https://www.readbyqxmd.com/read/28329588/ustekinumab-for-treatment-of-cutaneous-crohn-s-disease
#1
Rana Abdat, Alina Markova, Francis A Farraye, Michael K Lichtman
Cutaneous Crohn disease (CD) affecting the vulva, perineum, and perianal skin, is a rare entity, which may accompany or precede gastrointestinal CD. Vulvar involvement, if untreated, may ultimately require extensive surgery including vulvectomy to gain control of the disease. Both gastrointestinal and cutaneous CD respond to biologics, which block TNF. In addition, ustekinumab, which targets both IL-12 and IL-23 cytokines, is effective in patients with gastrointestinal CD who fail TNF blockade. However, it is unclear if ustekinumab is effective for cutaneous CD...
October 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329405/a-review-of-guselkumab-an-il-23-inhibitor-for-moderate-to-severe-plaque-psoriasis
#2
Z Nawas, M Hatch, E Ramos, M Liu, Y Tong, A Peranteau, S Tyring
Psoriasis is a chronic inflammatory skin disorder that affects 2% of the population. Evidence suggests that interleukin (IL)-23 plays a pivotal role in the pathogenesis of psoriasis. Guselkumab is a subcutaneously administered, humanized anti-IL23 monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis. Data from Phase I-III trials in this patient population reveal that guselkumab has proven to be superior to placebo or adalimumab based on achieving a Psoriasis Area and Severity Index (PASI) 90% reduction, or a static Physician Global Assessment (sPGA) score of 0 or 1 from baseline...
March 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28321152/th1-th17-related-cytokines-and-chemokines-and-their-implications-in-the-pathogenesis-of-pemphigus-vulgaris
#3
Rodolfo Pessato Timoteo, Marcos Vinicius da Silva, Camila Botelho Miguel, Djalma Alexandre Alves Silva, Jonatas Da Silva Catarino, Virmondes Rodrigues Junior, Helioswilton Sales-Campos, Carlo Jose Freire Oliveira
Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28319618/new-biologics-in-psoriasis-an-update-on-il-23-and-il-17-inhibitors
#4
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/28301545/implication-of-the-intestinal-microbiome-as-a-potential-surrogate-marker-of-immune-responsiveness-to-experimental-therapies-in-autoimmune-diabetes
#5
James C Needell, Charles A Dinarello, Diana Ir, Charles E Robertson, Sarah M Ryan, Miranda E Kroehl, Daniel N Frank, Danny Zipris
Type 1 diabetes (T1D) is an autoimmune proinflammatory disease with no effective intervention. A major obstacle in developing new immunotherapies for T1D is the lack of means for monitoring immune responsiveness to experimental therapies. The LEW1.WR1 rat develops autoimmunity following infection with the parvovirus Kilham rat virus (KRV) via mechanisms linked with activation of proinflammatory pathways and alterations in the gut bacterial composition. We used this animal to test the hypothesis that intervention with agents that block innate immunity and diabetes is associated with a shift in the gut microbiota...
2017: PloS One
https://www.readbyqxmd.com/read/28299442/interleukin-il-18-cooperatively-with-il-23-induces-prominent-inflammation-and-enhances-psoriasis-like-epidermal-hyperplasia
#6
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...
March 15, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28299384/impairment-of-systemic-dha-synthesis-affects-macrophage-plasticity-and-polarization-implications-for-dha-supplementation-during-inflammation
#7
Emanuela Talamonti, Anna M Pauter, Abolfazl Asadi, Alexander W Fischer, Valerio Chiurchiù, Anders Jacobsson
Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1 and M2 macrophages obtained from mice deficient of Elovl2 (Elovl2(-/-)), a key enzyme for DHA synthesis in mammals...
March 15, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28296821/protease-activated-receptor-1-plays-a-proinflammatory-role-in-colitis-by-promoting-th17-related-immunity
#8
Muhammad A Saeed, Garrett Z Ng, Jan Däbritz, Josef Wagner, Louise Judd, Jia-Xi Han, Poshmaal Dhar, Carl D Kirkwood, Philip Sutton
BACKGROUND: Proteolytic cleavage of protease-activated receptor 1 (PAR1) can result in potent downstream regulatory effects on inflammation. Although PAR1 is expressed throughout the gastrointestinal tract and activating proteases are increased in inflammatory bowel disease, the effect of PAR1 activation on colitis remains poorly understood, and has not previously been studied in pediatric disease. METHODS: Expression of PAR1 and inflammatory cytokines in colonic biopsies from pediatric patients with Crohn's disease exhibiting active moderate to severe colitis was measured by quantitative PCR...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28293399/up-regulation-of-tlr2-and-tlr4-in-high-mobility-group-box1-stimulated-macrophages-in-pulpitis-patients
#9
Javad Mahmoudi, Babak Sabermarouf, Behzad Baradaran, Leila Sadat-Hatamnezhad, Siamak Sandoghchian Shotorbani
OBJECTIVES: High Mobility Group Box1 (HMGB1) is a nonhistone, DNA-binding protein that serves a crucial role in regulating gene transcription and is involved in a variety of proinflammatory, extracellular activities. The aim of this study was to explore whether HMGB1 stimulation can up-regulate the expression of Toll-like Receptor 2 (TLR2) and Toll-like Receptor 4 (TLR4) on macrophages from pulpitis and to clarify the subsequent events involving Th17 cells and Th17 cell-associated cytokine changes...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28290522/nutritional-control-of-il-23-th17-mediated-autoimmune-disease-through-ho-1-stat3-activation
#10
Jürgen Brück, Julia Holstein, Ivana Glocova, Ursula Seidel, Julia Geisel, Toshio Kanno, Jin Kumagai, Naoko Mato, Stephan Sudowe, Katja Widmaier, Tobias Sinnberg, Amir S Yazdi, Franziska C Eberle, Kiyoshi Hirahara, Toshinori Nakayama, Martin Röcken, Kamran Ghoreschi
The nutritional curcumin (CUR) is beneficial in cell-mediated autoimmune diseases. The molecular mechanisms underlying this food-mediated silencing of inflammatory immune responses are poorly understood. By investigating antigen-specific immune responses we found that dietary CUR impairs the differentiation of Th1/Th17 cells in vivo during encephalomyelitis and instead promoted Th2 cells. In contrast, feeding CUR had no inhibitory effect on ovalbumin-induced airway inflammation. Mechanistically, we found that CUR induces an anti-inflammatory phenotype in dendritic cells (DC) with enhanced STAT3 phosphorylation and suppressed expression of Il12b and Il23a...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288964/il-38-overexpression-induces-anti-inflammatory-effects-in-mice-arthritis-models-and-in-human-macrophages-in-vitro
#11
Marie-Astrid Boutet, Aurélie Najm, Géraldine Bart, Régis Brion, Sophie Touchais, Valérie Trichet, Pierre Layrolle, Cem Gabay, Gaby Palmer, Frédéric Blanchard, Benoit Le Goff
OBJECTIVES: Interleukin (IL)-38 is a newly characterised cytokine that belongs to the IL-1 family. This cytokine is expressed in the rheumatoid arthritis (RA) synovial tissue and IL-38 deficient mice have exacerbated arthritis. Here, we analysed the effect of IL-38 overexpression in the joints of arthritic mice, in human macrophages and synovial fibroblasts in vitro. METHODS: Articular injections of an adeno-associated virus (AAV) 2/8 encoding IL-38 were performed in collagen-induced arthritis (CIA), K/BxN serum transfer-induced arthritis (STIA) and antigen-induced arthritis (AIA) in mice...
March 13, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28285360/kynurenic-acid-downregulates-il-17-1l-23-axis-in-vitro
#12
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/28284714/strain-specificities-in-cellular-and-molecular-immunopathogenic-mechanisms-underlying-development-of-experimental-autoimmune-encephalomyelitis-in-aged-rats
#13
Mirjana Nacka-Aleksić, Zorica Stojić-Vukanić, Ivan Pilipović, Ivana Vujnović, Biljana Bufan, Mirjana Dimitrijević, Gordana Leposavić
To understand strain-specificities of immune system in aged rats and their immunopathological implications, CD4+ T lymphocyte-mediated neuroinflammation in experimental autoimmune encephalomyelitis (EAE) was studied in two strains. Upon immunization for EAE, 22-24-month-old Albino Oxford (AO) rats developed milder neurological deficit of prolonged duration compared with their Dark Agouti (DA) counterparts. Consistently, they exhibited: (i) diminished neuroantigen-specific CD4+ T lymphocyte generation in draining lymph nodes (reflecting lower density of high-affinity IL-2 receptor complex on their surface and higher CD4+FoxP3+CD25+ regulatory cell frequency); (ii) less favorable spinal cord expression of CXCL12 and CCL2, and consequently diminished infiltration of neuroantigen-specific CD4+ T lymphocytes, including highly pathogenic IL-17+IFN-γ+ ones, and inflammatory monocytes into the spinal cord and (iii) subsequently impaired CD4+ T lymphocyte reactivation/survival and differentiation into highly pathogenic IL-17+ cells (reflecting downregulated expression of IL-1β, IL-6 and IL-23/p19)...
March 8, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28282579/interleukin-23-mediates-the-pathogenesis-of-lps-galn-induced-liver-injury-in-mice
#14
Suxia Bao, Qiang Zhao, Jianming Zheng, Ning Li, Chong Huang, Mingquan Chen, Qi Cheng, Mengqi Zhu, Kangkang Yu, Chenghai Liu, Guangfeng Shi
BACKGROUND: Interleukin-23 (IL-23) is required for T helper 17 (Th17) cell responses and IL-17 production in hepatitis B virus infection. A previous study showed that the IL-23/IL-17 axis aggravates immune injury in patients with chronic hepatitis B virus infection. However, the role of IL-23 in acute liver injury remains unclear. OBJECTIVE: The purpose of this study was to determine the role of the inflammatory cytokine IL-23 in lipopolysaccharide/d-galactosamine (LPS/GalN)-induced acute liver injury in mice...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28276258/an-interleukin-12-b-single-nucleotide-polymorphism-increases-il-12p40-production-and-is-associated-with-increased-disease-susceptibility-in-patients-with-relapsing-remitting-multiple-sclerosis
#15
Mohammad Reza Javan, Sarieh Shahraki, Amin Safa, Mohammad Reza Zamani, Arash Salmaninejad, Saeed Aslani
BACKGROUND: Through mounting genetic investigations, it has been established that IL12B and IL23R gene single nucleotide polymorphisms have significant associations with autoimmune diseases including inflammatory bowel disease, psoriasis, and ankylosing spondylitis. IL-12/IL-23 pathway plays a pivotal role in etiopathogenesis of multiple sclerosis (MS), suggested by studies both in patients and animal models. METHODS: In a case-control study, 145 MS patients and 200 healthy subjects were genotyped for polymorphisms in IL12B and IL23R genes using Real-Time PCR allelic discrimination approach...
March 9, 2017: Neurological Research
https://www.readbyqxmd.com/read/28275700/peripheral-inflammatory-markers-indicate-microstructural-damage-within-periventricular-white-matter-hyperintensities-in%C3%A2-alzheimer-s-disease-a-preliminary-report
#16
Walter Swardfager, Di Yu, Joel Ramirez, Hugo Cogo-Moreira, Gregory Szilagyi, Melissa F Holmes, Christopher J M Scott, Gustavo Scola, Pak C Chan, Jialun Chen, Parco Chan, Demetrios J Sahlas, Nathan Herrmann, Krista L Lanctôt, Ana C Andreazza, Jacqueline A Pettersen, Sandra E Black
INTRODUCTION: White matter hyperintensities (WMH) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear. METHODS: Inflammatory markers were assayed in 54 elderly participants (n = 16 with AD). Periventricular WMH were delineated from T1, T2/proton density, and fluid-attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28273557/curcumin-inhibiting-th17-cell-differentiation-by-regulating-the-metabotropic-glutamate-receptor-4-expression-on-dendritic-cells
#17
Guangming Zhao, Ying Liu, Xiaying Yi, Yupeng Wang, Song Qiao, Zhen Li, Jing Ni, Zhiqi Song
Th17 cells have been categorized as a new lineage of CD4+ T cells, and played a crucial role in the pathogenesis of numerous autoimmune disorders. Type 4 metabotropic glutamate receptor (mGluR4), a member of group III mGluRs, recently has been found to be expressed in many types of immune cells and mediate adaptive immunity. Curcumin has been shown to exhibit potent anti-inflammatory, antimutagenic and anticarcinogenic properties. For the past few years, it has gradually been regarded as an pluripotent immunomodulatory agent that can regulate the activation of immune cells...
March 4, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28273458/distinct-kinase-independent-role-of-ripk3-in-cd11c-mononuclear-phagocytes-in-cytokine-induced-tissue-repair
#18
Kenta Moriwaki, Sakthi Balaji, John Bertin, Peter J Gough, Francis Ka-Ming Chan
Receptor interacting protein kinase 3 (RIPK3) induces necroptosis, a type of regulated necrosis, through its kinase domain and receptor interacting protein (RIP) homotypic interaction motif (RHIM). In addition, RIPK3 has been shown to regulate NLRP3 inflammasome and nuclear factor κB (NF-κB) activation. However, the relative contribution of these signaling pathways to RIPK3-dependent inflammation in distinct immune effectors is unknown. To investigate these questions, we generated RIPK3-GFP reporter mice...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28271735/tildrakizumab-for-treating-psoriasis
#19
Marco Galluzzo, S D'Adamio, L Bianchi, M Talamonti
Agents that block inflammatory pathways other than tumor necrosis factor (TNF) have represented new options for treating psoriasis in recent years. IL-23 is involved in regulating Th17 cells and is a potent activator of keratinocyte proliferation. Targeting IL-23p19 alone may be a promising treatment approach in patients with moderate-to-severe chronic plaque psoriasis, with a downregulation of Th17 and Th22 cell responses, while IL-12 blockade is not required to achieve efficacy in these patients. Areas covered: The authors review and provide an update on tildrakizumab, a humanized IgG1 monoclonal antibody that blocks the p19 subunit of IL-23...
March 8, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28266782/systemic-immune-mechanisms-in-atopic-dermatitis-and-psoriasis-with-implications-for-treatment
#20
REVIEW
Emma Guttman-Yassky, James G Krueger, Mark G Lebwohl
Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases that negatively affect patients' quality of life. Although distinctions exist between these diseases, both are characterised by erythematous, thickened epidermal lesions that vary in intensity and affected body surface area. Early models of etiology attributed symptoms of both diseases to cutaneous inflammation at lesion sites, but recent studies have established that activated immune mediators in the circulation drive disease severity. Activation of T helper 2 (Th2) and Th22 cells in the circulation appears to be the principal initiator of acute AD pathology, with the emergence of Th1 and Th17/interleukin (IL)-23 pathway activation marking the transition to a chronic state...
March 7, 2017: Experimental Dermatology
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