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https://www.readbyqxmd.com/read/30021889/antibody-blockade-of-il-15-signaling-has-the-potential-to-durably-reverse-vitiligo
#1
Jillian M Richmond, James P Strassner, Lucio Zapata, Madhuri Garg, Rebecca L Riding, Maggi A Refat, Xueli Fan, Vincent Azzolino, Andrea Tovar-Garza, Naoya Tsurushita, Amit G Pandya, J Yun Tso, John E Harris
Vitiligo is an autoimmune disease of the skin mediated by CD8+ T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (TRM ) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)-deficient mice reportedly have impaired TRM formation, and IL-15 promotes TRM function ex vivo...
July 18, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29780671/protection-of-cultured-brain-endothelial-cells-from-cytokine-induced-damage-by-%C3%AE-melanocyte-stimulating-hormone
#2
András Harazin, Alexandra Bocsik, Lilla Barna, András Kincses, Judit Váradi, Ferenc Fenyvesi, Vilmos Tubak, Maria A Deli, Miklós Vecsernyés
The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells...
2018: PeerJ
https://www.readbyqxmd.com/read/29760713/human-leukocyte-antigen-class-i-alleles-and-the-autoreactive-t-cell-response-in-psoriasis-pathogenesis
#3
REVIEW
Jörg Christoph Prinz
Psoriasis is a complex immune-mediated inflammatory skin disease characterized by T-cell-driven epidermal hyperplasia. It occurs on a strong genetic predisposition. The human leukocyte antigen (HLA)-class I allele HLA-C*06:02 on psoriasis susceptibility locus 1 (PSORS1 on 6p21.3) is the main psoriasis risk gene. Other HLA-class I alleles encoding HLA molecules presenting overlapping peptide repertoires show associations with psoriasis as well. Outside the major histocompatibility complex region, genome-wide association studies identified more than 60 psoriasis-associated common gene variants exerting only modest individual effects...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29620037/association-of-interleukin-1-receptor-antagonist-intron-2-variable-number-of-tandem-repeats-polymorphism-with-vitiligo-susceptibility-in-gujarat-population
#4
Mala Singh, Mohmmad Shoab Mansuri, Shahnawaz D Jadeja, Yogesh S Marfatia, Rasheedunnisa Begum
Background: Vitiligo is a multifactorial, polygenic, autoimmune skin disorder caused by selective destruction of melanocytes. Interleukin 1 receptor antagonist intron 2 polymorphism was found to be associated with various autoimmune disorders. Aims: We aimed to investigate the association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism (rs2234663) with vitiligo to assess interleukin 1 receptor antagonist transcript levels and to perform possible genotype-phenotype correlation...
May 2018: Indian Journal of Dermatology, Venereology and Leprology
https://www.readbyqxmd.com/read/29312598/interleukin-22-participates-in-the-inflammatory-process-of-vitiligo
#5
Jinjin Dong, Xiaohong An, Hui Zhong, Yichuan Wang, Jing Shang, Jia Zhou
Vitiligo is an acquired depigmentary skin inflammatory disorder. The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, including interleukin (IL)-1β. IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. Among skin cell populations only keratinocytes are the major targets of IL-22. In the present study, we demonstrated that IL-22 promoting IL-1β secretion from keratinocytes via the Reactive oxygen species (ROS)-NOD-like receptor family, pyrin domain containing 3 (NLRP3)-caspase-1 pathway...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29241122/modulation-by-neighboring-cells-of-the-responses-and-fate-of-melanoma-cells-irradiated-with-uva
#6
Aleksandra Krzywon, Maria Widel, Krzysztof Fujarewicz, Magdalena Skonieczna, Joanna Rzeszowska-Wolny
UVA radiation, which accounts for about 95% of the solar spectrum, contributes to and may be the etiological factor of skin cancers of which malignant melanoma is the most aggressive. UVA causes oxidative stress in various types of cells in the skin, keratinocyte, melanocytes, and fibroblasts, which is responsible for its cytotoxic effect. Here we used a transwell system to explore how the responses of melanoma cells to a low dose of UVA (20kJ/m2 , ~10% of the minimal erythema dose) are influenced by neighboring co-cultured melanoma cells or fibroblasts...
January 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29042315/il-1%C3%AE-reduces-glua1-phosphorylation-and-its-surface-expression-during-memory-reconsolidation-and-%C3%AE-melanocyte-stimulating-hormone-can-modulate-these-effects
#7
Ivana Machado, Helgi B Schiöth, Mercedes Lasaga, Teresa Scimonelli
Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly, interleukin-1β (IL-1β) influences hippocampus-dependent memories. We previously reported that administration of IL-1β in dorsal hippocampus impaired contextual fear memory reconsolidation. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (α-MSH). Our results also demonstrated that IL-1β produced a significant decrease in glutamate release from dorsal hippocampus synaptosomes after reactivation of the fear memory...
January 2018: Neuropharmacology
https://www.readbyqxmd.com/read/28921219/effects-of-total-intravenous-anesthesia-with-propofol-on-immuno-endocrine-changes-during-surgical-stress
#8
Tetsuhiro Sakai, David O'Flaherty, Adolf H Giesecke, Akira Kudo, Kazuyoshi Hirota, Akitomo Matsuki
Endocrine factors and cytokines are crucial to host responses to stress and infection. Because surgery is a major stressful condition, it is necessary to understand the influence of specific anesthetic procedures on immune-endocrine responses. The purpose of this study was to compare total intravenous anesthesia with propofol with conventional inhalational anesthesia on circulating cortisol, adrenocorticotropic hormone (ACTH), prolactin, alpha-melanocyte-stimulating hormone (αMSH), and the cytokine, interleukin-6 (IL-6) in healthy patients undergoing tubal ligation...
September 1995: Journal of Anesthesia
https://www.readbyqxmd.com/read/28793632/active-nanofibrous-membrane-effects-on-gingival-cell-inflammatory-response
#9
David-Nicolas Morand, Olivier Huck, Laetitia Keller, Nadia Jessel, Henri Tenenbaum, Jean-Luc Davideau
Alpha-melanocyte stimulating hormone (α-MSH) is involved in normal skin wound healing and also has anti-inflammatory properties. The association of α-MSH to polyelectrolyte layers with various supports has been shown to improve these anti-inflammatory properties. This study aimed to evaluate the effects of nanofibrous membrane functionalized with α-MSH linked to polyelectrolyte layers on gingival cell inflammatory response. Human oral epithelial cells (EC) and fibroblasts (FB) were cultured on plastic or electrospun Poly-#-caprolactone (PCL) membranes with α-MSH covalently coupled to Poly-L-glutamic acid (PGA-α-MSH), for 6 to 24 h...
October 27, 2015: Materials
https://www.readbyqxmd.com/read/28778794/vitiligo-mechanistic-insights-lead-to-novel-treatments
#10
REVIEW
Michael L Frisoli, John E Harris
Vitiligo is an autoimmune disease of the skin characterized by patchy depigmentation. Current treatments are moderately effective at reversing disease by suppressing autoimmune inflammation in the skin and promoting melanocyte regeneration. Recent basic and translational research studies have significantly improved our understanding of disease pathogenesis, which is now leading to emerging treatment strategies based on targeted therapy. Here we discuss important clinical characteristics of vitiligo, current therapies and their limitations, advances in understanding disease pathogenesis, emerging targeted treatments, and strategies to optimize clinical trials to efficiently and effectively test these new treatments...
September 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28754339/il-1-receptor-knockout-mice-develop-epidermal-cysts-and-show-an-altered-innate-immune-response-after-exposure-to-uvb-radiation
#11
Nikhil N Kulkarni, Christopher A Adase, Ling-Juan Zhang, Andrew W Borkowski, Fengwu Li, James A Sanford, Daniel J Coleman, Carlos Aguilera, Arup K Indra, Richard L Gallo
In this study, we observed that mice lacking the IL-1 receptor (IL-1R) (IL1r-/- ) or deficient in IL1-β developed multiple epidermal cysts after chronic UVB exposure. Cysts that developed in IL1r-/- mice were characterized by the presence of the hair follicle marker Sox 9, keratins 10 and 14, and normal melanocyte distribution and retinoid X receptor-α expression. The increased incidence of cysts in IL1r-/- mice was associated with less skin inflammation as characterized by decreased recruitment of macrophages, and their skin also maintained epidermal barrier function compared with wild-type mice...
November 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28378637/primary-tr1-cells-from-metastatic-melanoma-eliminate-tumor-promoting-macrophages-through-granzyme-b-and-perforin-dependent-mechanisms
#12
Hongxia Yan, Ping Zhang, Xue Kong, Xianglian Hou, Li Zhao, Tianhang Li, Xiaozhou Yuan, Hongjun Fu
In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28247923/regulatory-t-cell-cytokines-in-patients-with-nonsegmental-vitiligo
#13
Mehtap Kidir, Ayse A Karabulut, Mustafa E Ercin, Pınar Atasoy
In the etiopathogenesis of vitiligo, the role of suppressor cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), associated with regulatory T-cells (Treg) is not completely known. In this study, the role of Treg-cell functions in the skin of patients with nonsegmental vitiligo was investigated. Lesional and nonlesional skin samples from 30 adult volunteers ranging in age from 18 to 36 years with nonsegmental vitiligo were compared with normal skin area excision specimens of 30 benign melanocytic nevus cases as controls...
May 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#14
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+ CD49a+ Trm cells produced interferon-γ, whereas CD8+ CD49a- Trm cells produced interleukin-17 (IL-17). In addition, CD8+ CD49a+ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28164623/decreased-synovial-fluid-%C3%AE-melanocyte-stimulating-hormone-%C3%AE-msh-levels-reflect-disease-severity-in-patients-with-posttraumatic-ankle-osteoarthritis
#15
Guangyu Liu, Yunzhen Chen, Guichun Wang, Jianbing Niu
BACKGROUND: α-Melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin peptide, has been demonstrated to have anti-inflammation effects and protect against cartilage damage. Objective In this study, we aimed to investigate whether α-MSH in ankle joint synovial fluid is associated with the disease severity of posttraumatic ankle osteoarthritis (PTAOA). METHODS: 66 PTAOA patients undergoing ankle arthroscopical debridement or ankle joint replacement were enrolled in the study...
August 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28103316/alpha-melanocyte-stimulating-hormone-protects-against-cytokine-induced-barrier-damage-in-caco-2-intestinal-epithelial-monolayers
#16
Judit Váradi, András Harazin, Ferenc Fenyvesi, Katalin Réti-Nagy, Péter Gogolák, György Vámosi, Ildikó Bácskay, Pálma Fehér, Zoltán Ujhelyi, Gábor Vasvári, Eszter Róka, David Haines, Mária A Deli, Miklós Vecsernyés
Alpha-melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and permeability for marker molecules...
2017: PloS One
https://www.readbyqxmd.com/read/28003381/il-23-inhibits-melanoma-development-by-augmenting-dna-repair-and-modulating-t-cell-subpopulations
#17
Tahseen H Nasti, J Barry Cochran, Raj V Vachhani, Kristopher McKay, Yuko Tsuruta, Mohammad Athar, Laura Timares, Craig A Elmets
In animal models, IL-12 and IL-23 participate in the development of malignant neoplasms of keratinocytes. However, the role of these cytokines in pigmented lesion development and their progression to melanoma has received little attention. IL-12p35, IL-23p19, and IL-12/IL-23p40 knockout mice on a C3H/HeN background, subjected to a melanomagenesis protocol, demonstrated profound differences in susceptibility to nevus initiation, transformation, tumorigenicity, and metastatic potential. IL-23 was found to be essential for melanocyte homeostasis, whereas IL-12 supported nevus development...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27635239/recent-advances-in-understanding-vitiligo
#18
REVIEW
Prashiela Manga, Nada Elbuluk, Seth J Orlow
Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation...
2016: F1000Research
https://www.readbyqxmd.com/read/27567084/cross-talk-between-interferon-gamma-and-interleukin-18-in-melanogenesis
#19
Jia Zhou, Jingjing Ling, Yong Wang, Jing Shang, Fengfeng Ping
Skin is the largest organ in our body and strategically placed to provide a metabolically active biological barrier against a range of noxious stressors. A lot of inflammatory cytokines, which are increased after ultraviolet (UV) irradiation produced by keratinocytes or other immunocytes, are closely related to pigmentary changes, including interleukin-18 (IL-18) and interferon-γ (IFN-γ). In this study, the effect of cross-talk between IL-18 and IFN-γ on melanogenesis was investigated. Treatment with IL-18 resulted in a dose-dependent increase of melanogenesis, while IFN-γ made an opposite effect...
October 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27396757/%C3%AE-msh-modulates-cell-adhesion-and-inflammatory-responses-of-synovial-fibroblasts-from-osteoarthritis-patients
#20
Markus Böhm, Mara Apel, Torsten Lowin, Julia Lorenz, Zsuzsa Jenei-Lanzl, Silvia Capellino, Heba Dosoki, Thomas A Luger, Rainer H Straub, Susanne Grässel
INTRODUCTION: The synovium is a target for neuropeptides. Melanocortins have attained particular attention as they elicit antiinflammatory effects. Although synovial fluid from patients with rheumatic diseases contains α-melanocyte-stimulating hormone (α-MSH) it is unknown whether synovial fibroblasts generate α-MSH and respond to melanocortins. METHODS: Synovial tissue was obtained from osteoarthritis (OA) patients. Cells were isolated and prepared either as primary mixed synoviocytes or propagated as synovial fibroblasts (OASFs)...
September 15, 2016: Biochemical Pharmacology
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