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https://www.readbyqxmd.com/read/29021166/an-analysis-of-il-36-signature-genes-and-individuals-with-il1rl2-knockout-mutations-validates-il-36-as-a-psoriasis-therapeutic-target
#1
Satveer K Mahil, Marika Catapano, Paola Di Meglio, Nick Dand, Helena Ahlfors, Ian M Carr, Catherine H Smith, Richard C Trembath, Mark Peakman, John Wright, Francesca D Ciccarelli, Jonathan N Barker, Francesca Capon
Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (TH17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28975626/il-36-in-hidradenitis-suppurativa-evidence-for-a-distinctive-pro-inflammatory-role-and-a-key-factor-in-the-development-of-an-inflammatory-loop
#2
S Hessam, M Sand, T Gambichler, M Skrygan, I Rüddel, F G Bechara
BACKGROUND: A possible regulatory involvement of the interleukin (IL)-36 family in inflammatory diseases has been suggested. OBJECTIVES: To analyze the expression of IL-36α, β, γ, and the antagonistic cytokines IL-36Ra, IL-37, and IL38 in the skin of hidradenitis suppurativa (HS) patients. METHODS: Skin samples from lesional and corresponding perilesional HS skin, and from healthy controls were included in this study and analyzed by quantitative real-time RT-PCR...
October 4, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28967976/highlighting-interleukin-36-signalling-in-plaque-psoriasis-and-pustular-psoriasis
#3
Kazuhisa Furue, Kazuhiko Yamamura, Gaku Tsuji, Chikage Mitoma, Hiroshi Uchi, Takeshi Nakahara, Makiko Kido-Nakahara, Takafumi Kadono, Masutaka Furue
Plaque psoriasis and pustular psoriasis are overlapping, but distinct, disorders. The therapeutic response to biologics supports the pivotal role of the tumour necrosis alpha (TNF-α)/ interleukin (IL)-23/IL-17/IL-22 axis in the pathogenesis of these disorders. Recently, functional activation of the IL-36 receptor (IL-36R) was discovered to be another driving force in the pathogenesis of psoriasis. This was first highlighted by the discovery that a loss-of-function mutation of the IL-36R antagonist (IL-36Ra) causes pustular psoriasis...
October 2, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28942884/overexpression-of-il-38-protein-in-anticancer-drug-induced-lung-injury-and-acute-exacerbation-of-idiopathic-pulmonary-fibrosis
#4
Masaki Tominaga, Masaki Okamoto, Tomotaka Kawayama, Masanobu Matsuoka, Shinjiro Kaieda, Yuki Sakazaki, Takashi Kinoshita, Daisuke Mori, Akira Inoue, Tomoaki Hoshino
BACKGROUND: Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. METHODS: To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5)...
September 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28924372/il-36%C3%AE-inhibits-differentiation-and-induces-inflammation-of-keratinocyte-via-wnt-signaling-pathway-in-psoriasis
#5
Wenming Wang, Xiaoling Yu, Chao Wu, Hongzhong Jin
Psoriasis is a common inflammatory skin disease characterized by abnormal keratinocyte inflammation and differentiation that has a major impact on patients' quality of life. IL-36γ, a member of IL-36 cytokine family, is highly expressed in psoriasis and plays an important role in inflammation response and differentiation. However, the function of IL-36γ in differentiation and inflammation of keratinocyte in psoriasis has not been clearly identified. Thus, this study aimed to investigate the role of IL-36γ on differentiation and inflammation in HaCaT cells...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28869889/il-36-induces-cytokine-il-6-and-chemokine-cxcl8-expression-in-human-lung-tissue-cells-implications-for-pulmonary-inflammatory-responses
#6
Juan Zhang, Yibing Yin, Xue Lin, Xingxing Yan, Yun Xia, Liping Zhang, Ju Cao
IL-36α, IL-36β and IL-36γ are cytokine members of IL-1 family. Although IL-36 expression was observed in human lung during pulmonary infections, it remains unknown whether IL-36 could act directly on lung tissue cells during pulmonary inflammatory responses. In this study, we showed that IL-36 receptor was expressed in human lung fibroblasts and bronchial epithelial cells. Correspondingly, IL-36α, IL-36β or IL-36γ up-regulated gene expression of cytokine IL-6 and chemokine CXCL8 in human lung fibroblasts and bronchial epithelial cells, and promoted IL-6 and CXCL8 release from human lung fibroblasts and bronchial epithelial cells...
September 1, 2017: Cytokine
https://www.readbyqxmd.com/read/28857172/interleukin-36-receptor-mediates-the-crosstalk-between-plasma-cells-and-synovial-fibroblasts
#7
Verena Schmitt, Madelaine Hahn, Verena Kästele, Olga Wagner, Maximilian Wiendl, Anja Derer, Adriano Taddeo, Stefanie Hahne, Andreas Radbruch, Hans-Martin Jäck, Wolfgang Schuh, Dirk Mielenz, Steffen Gay, Georg Schett, Axel J Hueber, Silke Frey
The IL-1 family member IL-36α has proinflammatory and pathogenic properties in psoriasis. IL-36α binds to the IL-36 receptor leading to nuclear factor kappa B/mitogen activated protein kinase mediated cytokine release. The IL-36R antagonist prevents recruitment of IL-1 receptor accessory protein and therefore IL-36-dependent cell activation. In inflamed human tissue, we previously could show that resident B cells and plasma cells (PC) express IL-36α. Further, fibroblast-like synoviocytes (FLS) produced proinflammatory cytokines upon IL-36α-stimulation...
August 31, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28852851/il-36-cytokines-are-increased-in-acne-and-hidradenitis-suppurativa
#8
Roberta Di Caprio, Anna Balato, Giuseppina Caiazzo, Serena Lembo, Annunziata Raimondo, Gabriella Fabbrocini, Giuseppe Monfrecola
Interleukin (IL)-36 cytokines are new members of the IL-1 family, which include pro-inflammatory factors, IL-36α, IL-36β and IL-36γ, and a natural receptor antagonist IL-36Ra. Over recent years, much has been learned on their important functions in the regulation of immune response and, especially, on their role in many inflammatory skin diseases. However, to date, no data have been reported on their possible involvement in acne and hidradenitis suppurativa (HS). Here, we have shown that IL-36α, IL-36β, and IL-36γ are increased in lesional skin of acne and HS, highlighting their possible pathogenetic contribution to these two skin conditions...
August 29, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28812775/polymorphic-light-eruption-and-il-1-family-members-any-difference-with-allergic-contact-dermatitis
#9
S Lembo, G Caiazzo, N Balato, G Monfrecola, V Patra, P Wolf, A Balato
Polymorphic light eruption (PLE) is described as a delayed-type hypersensitivity reaction (DTHR) toward a de novo light-induced antigen, yet to be identified. In effect, the inflammatory pathways of PLE and allergic contact dermatitis (ACD) share common patterns in terms of the mediators involved from the innate and adaptive immune system participating in the DTHR. As we have previously highlighted the role of interleukin (IL)-1 family members in ACD, we hypothesised that the same mediators could have similar functions in PLE...
September 13, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28811383/interleukin-36-cytokines-may-overcome-microbial-immune-evasion-strategies-that-inhibit-interleukin-1-family-signaling
#10
REVIEW
Liselotte E Jensen
Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36α, IL-36β and IL-36γ, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28798075/cytokines-of-the-il-1-family-recognized-targets-in-chronic-inflammation-underrated-in-organ-transplantations
#11
REVIEW
Ilja Striz
Interleukin 1 (IL-1) family is a group of cytokines with multiple local and systemic effects, which regulates both innate and adaptive immune responses. Generally, most IL-1 family cytokines express prevailing pro-inflammatory activities (IL-1α, IL-1β, IL-18, IL-33, IL-36 α, β, γ), whereas others are anti-inflammatory (IL-1Ra (IL-1 receptor antagonist), IL-36Ra, IL-38, IL-37). In addition to their immunomodulatory roles, some of them are also involved in the physiological modulation of homeostatic processes and directly affect mRNA transcription...
September 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28774595/interleukin-36%C3%AE-induced-by-the-tlr3-slug-vdr-axis-promotes-wound-healing-via-reg3a
#12
Ziwei Jiang, Yuanqi Liu, Changwei Li, Leilei Chang, Wang Wang, Zhenhua Wang, Xiaoguang Gao, Bernhard Ryffel, Yelin Wu, Yuping Lai
Interleukin-36 (IL-36) family members are highly expressed in hyperproliferative keratinocytes and play an important role in the pathogenesis of skin diseases such as psoriasis. However, whether and how IL-36 cytokines are induced to promote wound healing remains unknown. Here we demonstrated that skin injury increased the expression of IL-36γ to promote wound healing. Mechanistically, the expression of IL-36γ was induced by RNAs from damaged cells via the activation of Toll-like receptor 3 (TLR3) and TIR-domain-containing adapter-inducing interferon-β (TRIF) followed by the induction of a zinc finger protein SLUG to abrogate the inhibitory effect of vitamin D receptor (VDR) on the promoter of IL-36γ gene...
July 31, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28726542/generation-and-functional-characterization-of-anti-human-and-anti-mouse-il-36r-antagonist-monoclonal-antibodies
#13
Rajkumar Ganesan, Ernest L Raymond, Detlev Mennerich, Joseph R Woska, Gary Caviness, Christine Grimaldi, Jennifer Ahlberg, Rocio Perez, Simon Roberts, Danlin Yang, Kavita Jerath, Kristopher Truncali, Lee Frego, Eliud Sepulveda, Priyanka Gupta, Su-Ellen Brown, Michael D Howell, Keith A Canada, Rachel Kroe-Barrett, Jay S Fine, Sanjaya Singh, M Lamine Mbow
Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP)...
October 2017: MAbs
https://www.readbyqxmd.com/read/28724920/interleukin-36%C3%AE-provides-protection-against-hsv-1-infection-but-does-not-modulate-initiation-of-adaptive-immune-responses
#14
Katelynn A Milora, Siva R Uppalapati, Julio C Sanmiguel, Wei Zou, Liselotte E Jensen
Interleukin-36 (IL-36) represents three cytokines, IL-36α, IL-36β and IL-36γ, which bind to the same receptor, IL-1RL2; however, their physiological function(s) remain poorly understood. Here, the role of IL-36 in immunity against HSV-1 was examined using the flank skin infection mouse model. Expression analyses revealed increased levels of IL-36α and IL-36β mRNA in infected skin, while constitutive IL-36γ levels remained largely unchanged. In human keratinocytes, IL-36α mRNA was induced by HSV-1, while IL-1β and TNFα increased all three IL-36 mRNAs...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611508/correlation-between-il36%C3%AE-and-il17-and-activity-of-the-disease-in-selected-autoimmune-blistering-diseases
#15
Agnieszka Żebrowska, Anna Woźniacka, Katarzyna Juczyńska, Kamila Ociepa, Elżbieta Waszczykowska, Izabela Szymczak, Rafał Pawliczak
Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28602023/increased-expression-of-the-interleukin-36-cytokines-in-lesions-of-hidradenitis-suppurativa
#16
R Thomi, M Kakeda, N Yawalkar, C Schlapbach, R E Hunger
BACKGROUND: Hidradenitis suppurativa (HS) is a recalcitrant chronic skin disease with poorly understood immunopathogenic mechanisms. Previous studies reported that the interleukin-36 (IL-36) cytokines [IL-36α, IL-36β, IL-36γ and IL-36 receptor antagonists (IL-36RA)] are important players in the pathogenesis of psoriasis (PS). OBJECTIVE: We aim to determine whether the IL-36 cytokines are upregulated in patients with HS. For this purpose, we analysed local expression and systemic levels of the IL-36 cytokines in patients with HS and compared the results to healthy donors and patients with PS...
June 11, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28374518/neutrophil-extracellular-traps-can-serve-as-platforms-for-processing-and-activation-of-il-1-family-cytokines
#17
Danielle M Clancy, Conor M Henry, Graeme P Sullivan, Seamus J Martin
Activated neutrophils can undergo a mode of regulated cell death, called NETosis, that results in the extrusion of chromatin into the extracellular space, thereby acting as extracellular traps for microorganisms. Neutrophil-derived extracellular traps (NETs) are comprised of DNA decorated with histones, antimicrobial proteins and neutrophil granule proteases, such as elastase and cathepsin G (Cat G). NET-associated factors are thought to enhance the antimicrobial properties of these structures and localisation of antimicrobial molecules on NETs may serve to increase their local concentration...
June 2017: FEBS Journal
https://www.readbyqxmd.com/read/28327619/il-36%C3%AE-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-via-nf%C3%AE%C2%BAb-activation-and-stat-transcription-factors
#18
A Harusato, H Abo, V L Ngo, S W Yi, K Mitsutake, S Osuka, J E Kohlmeier, J D Li, A T Gewirtz, A Nusrat, T L Denning
Regulatory and effector T helper (Th) cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4(+) T cells to potently inhibit Foxp3-expressing induced regulatory T cell (Treg) development, while concomitantly promoting the differentiation of Th9 cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway...
November 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28196704/toll-like-receptor-4-antagonist-tak-242-inhibits-autoinflammatory-symptoms-in-ditra
#19
Akitaka Shibata, Kazumitsu Sugiura, Yasuhide Furuta, Yoshiko Mukumoto, Osamu Kaminuma, Masashi Akiyama
BACKGROUND: IL36RN encodes the IL-36 receptor antagonist (IL-36Ra), and loss-of-function mutations in IL36RN define a recessively inherited autoinflammatory disease named "deficiency of IL-36Ra" (DITRA). DITRA causes systemic autoinflammatory diseases, including generalized pustular psoriasis (GPP), an occasionally life-threatening disease that is characterized by widespread sterile pustules on the skin, fever and other systemic symptoms. GPP can present at any age, and provocative factors include various infections, medicines and pregnancy...
February 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28179433/il-36-signaling-facilitates-activation-of-the-nlrp3-inflammasome-and-il-23-il-17-axis-in-renal-inflammation-and-fibrosis
#20
Hsi-Hua Chi, Kuo-Feng Hua, Yu-Chuan Lin, Ching-Liang Chu, Chih-Yu Hsieh, Yu-Juei Hsu, Shuk-Man Ka, Yu-Ling Tsai, Feng-Cheng Liu, Ann Chen
IL-36 cytokines are proinflammatory and have an important role in innate and adaptive immunity, but the role of IL-36 signaling in renal tubulointerstitial lesions (TILs), a major prognostic feature of renal inflammation and fibrosis, remains undetermined. In this study, increased IL-36α expression detected in renal biopsy specimens and urine samples from patients with renal TILs correlated with renal function impairment. We confirmed the increased expression of IL-36α in the renal tubular epithelial cells of a mouse model of unilateral ureteral obstruction (UUO) and related cell models using mechanically induced pressure, oxidative stress, or high mobility group box 1...
July 2017: Journal of the American Society of Nephrology: JASN
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