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https://www.readbyqxmd.com/read/29914927/regulation-of-the-peptidoglycan-amidase-pglyrp2-in-epithelial-cells-by-il-36%C3%AE
#1
Glen M Scholz, Jacqueline E Heath, Jiamin Aw, Eric C Reynolds
IL-36 cytokines are important regulators of mucosal homeostasis and inflammation. We have previously established that oral epithelial cells upregulate IL-36γ expression in response to the bacterial pathogen Porphyromonas gingivalis Here, we have established that IL-36γ can stimulate the gene expression of mechanistically-distinct antimicrobial proteins, including the peptidoglycan amidase PGLYRP2, in oral epithelial cells (e.g. TIGK cells). PGLYRP2 gene expression was not stimulated by either IL-17 or IL-22, and thus demonstrating selectivity in the regulation of PGLYRP2 by IL-36γ...
June 18, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29891557/il-36-and-il-1-il-17-drive-immunity-to-oral-candidiasis-via-parallel-mechanisms
#2
Akash H Verma, Hanna Zafar, Nicole O Ponde, Olivia W Hepworth, Diksha Sihra, Felix E Y Aggor, Joseph S Ainscough, Jemima Ho, Jonathan P Richardson, Bianca M Coleman, Bernhard Hube, Martin Stacey, Mandy J McGeachy, Julian R Naglik, Sarah L Gaffen, David L Moyes
Protection against microbial infection by the induction of inflammation is a key function of the IL-1 superfamily, including both classical IL-1 and the new IL-36 cytokine families. Candida albicans is a frequent human fungal pathogen causing mucosal infections. Although the initiators and effectors important in protective host responses to C. albicans are well described, the key players in driving these responses remain poorly defined. Recent work has identified a central role played by IL-1 in inducing innate Type-17 immune responses to clear C...
June 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29891552/opposing-effects-of-il-1ra-and-il-36ra-on-innate-immune-response-to-pseudomonas-aeruginosa-infection-in-c57bl-6-mouse-corneas
#3
Nan Gao, Rao Me, Chenyang Dai, Berhane Seyoum, Fu-Shin X Yu
Pseudomonas aeruginosa keratitis is characterized by severe corneal ulceration and may lead to blindness if not treated properly in a timely manner. Although the roles of the IL-1 subfamily of cytokines are well established, as a newly discovered subfamily, IL-36 cytokine regulation, immunological relevance, and relation with IL-1 cytokines in host defense remain largely unknown. In this study, we showed that P. aeruginosa infection induces the expression of IL-36α and IL-36γ, as well as IL-1β and secreted IL-1Ra (sIL-1Ra), but not IL-36Ra...
June 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29889692/spondyloarthritis-new-insights-into-clinical-aspects-translational-immunology-and-therapeutics
#4
Charlie Bridgewood, Abdulla Watad, Richard J Cuthbert, Dennis McGonagle
PURPOSE OF REVIEW: The spondyloarthopathies (SpA), which encompass related diseases that were originally viewed as autoimmune, are now known to have a strong innate immune or autoinflammatory initiation phase characterized by disease localization to tissue-specific sites based on the nuances and microanatomy and immunology of those sites. This review covers recent translational advances in the field of SpA. RECENT FINDINGS: Imaging studies in SpA continue to add support for the pivotal role of enthesitis in disease initiation and expression...
June 9, 2018: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29852521/generalized-pustular-psoriasis-a-model-disease-for-specific-targeted-immunotherapy-systematic-review
#5
REVIEW
Alexander Boehner, Alexander A Navarini, Kilian Eyerich
Generalized pustular psoriasis (GPP) psoriasis is a rare, multisystemic skin disease characterized by recurrent episodes of pustulation. GPP can be life-threatening and is often difficult to treat. In the era of precision medicine in dermatology, GPP stands exemplary for both challenges and chances - while new treatments offer great hope, there is urgent need for better definition and stratification of this severe and heterogeneous disease. Our objective was to systematically review the literature for evidence of efficacy of targeted immunotherapy and their mode of action in the context of clinical phenotype, classification and pathogenesis of adult GPP...
May 31, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29803800/ichthyosis-molecular-fingerprinting-shows-profound-th17-skewing-and-a-unique-barrier-genomic-signature
#6
Kunal Malik, Helen He, Thy Nhat Huynh, Gary Tran, Kelly Mueller, Kristina Doytcheva, Yael Renert-Yuval, Tali Czarnowicki, Shai Magidi, Margaret Chu, Yeriel D Estrada, Huei-Chi Wen, Xiangyu Peng, Hui Xu, Xiuzhong Zheng, James G Krueger, Amy S Paller, Emma Guttman-Yassky
BACKGROUND: Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotyping of ichthyotic skin could suggest much-needed pathogenesis-based therapy. OBJECTIVE: To profile the molecular fingerprint of the most common orphan ichthyoses. METHODS: Gene, protein, and serum studies were performed on skin and blood samples from 29 patients (congenital ichthyosiform erythroderma/CIE, n=9; lamellar ichthyosis/LI, n=8; epidermolytic ichthyosis/EI, n=8; and Netherton syndrome/NS, n=4), as well as age-matched healthy controls (n=14), psoriasis (n=30), and atopic dermatitis/AD (n=16) patients...
May 24, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29794016/il-36%C3%AE-from-skin-resident-cells-plays-an-important-role-in-the-pathogenesis-of-imiquimod-induced-psoriasiform-dermatitis-by-forming-a-local-autoamplification-loop
#7
Yuriko Hashiguchi, Rikio Yabe, Soo-Hyun Chung, Masanori A Murayama, Kaori Yoshida, Kenzo Matsuo, Sachiko Kubo, Shinobu Saijo, Yuumi Nakamura, Hiroyuki Matsue, Yoichiro Iwakura
IL-36α (gene symbol Il1f6 ), a member of the IL-36 family, is closely associated with inflammatory diseases, including colitis and psoriasis. In this study, we found that Il1f6 -/- mice developed milder psoriasiform dermatitis upon treatment with imiquimod, a ligand for TLR ligand 7 (TLR7) and TLR8, whereas Il1f6 -/- mice showed similar susceptibility to dextran sodium sulfate-induced colitis to wild-type mice. These effects were observed in both cohoused and separately housed conditions, and antibiotic treatment did not cancel the resistance of Il1f6 -/- mice to imiquimod-induced dermatitis...
May 23, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29760082/a-cytokine-network-involving-il-36%C3%AE-il-23-and-il-22-promotes-antimicrobial-defense-and-recovery-from-intestinal-barrier-damage
#8
Vu L Ngo, Hirohito Abo, Estera Maxim, Akihito Harusato, Duke Geem, Oscar Medina-Contreras, Didier Merlin, Andrew T Gewirtz, Asma Nusrat, Timothy L Denning
The gut epithelium acts to separate host immune cells from unrestricted interactions with the microbiota and other environmental stimuli. In response to epithelial damage or dysfunction, immune cells are activated to produce interleukin (IL)-22, which is involved in repair and protection of barrier surfaces. However, the specific pathways leading to IL-22 and associated antimicrobial peptide (AMP) production in response to intestinal tissue damage remain incompletely understood. Here, we define a critical IL-36/IL-23/IL-22 cytokine network that is instrumental for AMP production and host defense...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29757591/evaluating-serum-levels-of-il-33-il-36-il-37-and-gene-expression-of-il-37-in-patients-with-psoriasis-vulgaris
#9
Mojtaba Sehat, Rezvan Talaei, Ehsan Dadgostar, Hassan Nikoueinejad, Hossein Akbari
Serum levels of interleukin (IL)-33, IL-36 and IL-37 have been reported to be up-regulated in various T helper (Th)1/Th17 mediated autoimmune/inflammatory diseases. Although IL-33 and IL-36 expression are increased in skin lesions of patients with psoriasis, their serum levels in such patients have not yet been adequately studied. We aimed to evaluate serum level of IL-33, IL-36 and IL-37 cytokines and IL-37 gene expression in patients with autoimmune/inflammatory disease of psoriasis and to explore their correlation with disease severity...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29744290/identification-of-small-molecule-elastase-inhibitors-as-antagonists-of-il-36-cytokine-activation
#10
Graeme P Sullivan, Pavel B Davidovich, Sylvia Sura-Trueba, Ekaterina Belotcerkovskaya, Conor M Henry, Danielle M Clancy, Anna Zinoveva, Tazhir Mametnabiev, Alexander V Garabadzhiu, Seamus J Martin
IL-1 family cytokines act as apical initiators of inflammation in many settings and can promote the production of a battery of inflammatory cytokines, chemokines and other inflammatory mediators in diverse cell types. IL-36α, IL-36β and IL-36γ, which belong to the extended IL-1 family, have been implicated as key initiators of skin inflammation in psoriasis. IL-36γ is highly upregulated in lesional skin from psoriatic individuals, and heritable mutations in the natural IL-36 receptor antagonist result in a severe form of psoriasis...
May 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29742056/a-dermatologic-perspective-on-autoinflammatory-diseases
#11
REVIEW
Angelo Valerio Marzano, Giovanni Damiani, Giovanni Genovese, Marco Gattorno
Autoinflammatory diseases (AIDs) encompass a heterogeneous group of disorders pathogenetically related to an abnormal activation of the innate immunity and clinically characterised by aseptic inflammation in the affected organs in the absence of high titer of circulating autoantibodies or autoreactive T cells. In classic monogenic AIDs, the skin is frequently involved with a wide range of cutaneous lesions. Monogenic AIDs result from different mutations in a single gene, which regulates the innate immunity...
January 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29655629/intramuscular-vaccination-of-guinea-pigs-with-the-live-attenuated-human-herpes-simplex-vaccine-vc2-stimulates-a-transcriptional-profile-of-vaginal-th17-and-regulatory-tr1-responses
#12
Brent A Stanfield, Paul J F Rider, John Caskey, Fabio Del Piero, Konstantin G Kousoulas
Herpes simplex virus is a common causative agent of oral and genital diseases. Novel vaccines and therapeutics are needed to combat herpes infections especially after the failure of subunit vaccines in human clinical trials. We have shown that the live-attenuated HSV-1 VC2 vaccine strain is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. The guinea pig represents the best small animal model of genital HSV-2 disease...
May 11, 2018: Vaccine
https://www.readbyqxmd.com/read/29644902/interleukin-il-36-gamma-induces-mucin-5ac-oligomeric-mucus-gel-forming-expression-via-il-36-receptor-extracellular-signal-regulated-kinase-1-and-2-and-p38-nuclear-factor-kappa-light-chain-enhancer-of-activated-b-cells-in-human-airway-epithelial-cells
#13
Chang Hoon Bae, Yoon Seok Choi, Hyung Gyun Na, Si-Youn Song, Yong-Dae Kim
BACKGROUND: Mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) expression is significantly increased in allergic and inflammatory airway diseases. Interleukin (IL) 36 gamma is predominantly expressed in airway epithelial cells and plays an important role in innate and adaptive immune responses. IL-36 gamma is induced by many inflammatory mediators, including cytokines and bacterial and viral infections. However, the association between IL-36 gamma and mucin secretion in human airway epithelial cells has not yet been fully investigated...
March 2018: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/29571080/increased-serum-il-36%C3%AE-and-il-36%C3%AE-levels-in-patients-with-systemic-lupus-erythematosus-association-with-disease-activity-and-arthritis
#14
Shao-Zhen Mai, Chi-Jun Li, Xiao-Ying Xie, Hui Xiong, Min Xu, Fan-Qin Zeng, Qing Guo, Yan-Fang Han
IL-36 cytokines (IL-36Ra, IL-36α, IL-36β and IL-36γ) belong to the IL-1 family and have been linked to several autoimmune diseases. However, little is known about the relationships between systemic lupus erythematosus (SLE) and IL-36 cytokines. In this study, serum IL-36 cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA), and their associations with SLE-related parameters were analyzed in 72 SLE patients and 63 healthy controls. Additionally, IL-36 cytokine mRNA levels were assessed in 30 of 72 SLE patients and 20 of 63 healthy controls using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR)...
May 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29565192/pharmacotherapeutic-approaches-for-treating-psoriasis-in-difficult-to-treat-areas
#15
REVIEW
Dario Kivelevitch, Jillian Frieder, Ian Watson, So Yeon Paek, M Alan Menter
Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients' quality of life and requires an adequate selection of treatments. Areas covered: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature...
April 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29554104/the-severity-of-imiquimod-induced-mouse-skin-inflammation-is-independent-of-endogenous-il-38-expression
#16
Jennifer Palomo, Sabina Troccaz, Dominique Talabot-Ayer, Emiliana Rodriguez, Gaby Palmer
The IL-1 cytokine family includes eleven members, among which Il-36α, β and γ, IL-36Ra and IL-38. The IL-36 cytokines are involved in the pathogenesis of psoriasis. IL-38 is also expressed in the skin and was previously proposed to act as an IL-36 antagonist. In this study, we thus examined expression and function of Il-38 in a mouse model of imiquimod (IMQ)-induced skin inflammation. Il-38 mRNA was detected in the epidermis and in primary mouse keratinocytes, but not in dermal fibroblasts. At the peak of IMQ-induced inflammation, skin Il-38 mRNA levels were reduced, whereas Il-36ra mRNA expression increased...
2018: PloS One
https://www.readbyqxmd.com/read/29539422/extracellular-neutrophil-proteases-are-efficient-regulators-of-il-1-il-33-and-il-36-cytokine-activity-but-poor-effectors-of-microbial-killing
#17
Danielle M Clancy, Graeme P Sullivan, Hannah B T Moran, Conor M Henry, Emer P Reeves, Noel G McElvaney, Ed C Lavelle, Seamus J Martin
Neutrophil granule proteases are thought to function as anti-microbial effectors, cooperatively hydrolyzing microorganisms within phagosomes, or upon deployment into the extracellular space. However, evidence also suggests that neutrophil proteases play an important role in the coordination and escalation of inflammatory reactions, but how this is achieved has been obscure. IL-1 family cytokines are important initiators of inflammation and are typically released via necrosis but require proteolytic processing for activation...
March 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29515113/suppressing-il-36-driven-inflammation-using-peptide-pseudosubstrates-for-neutrophil-proteases
#18
Graeme P Sullivan, Conor M Henry, Danielle M Clancy, Tazhir Mametnabiev, Ekaterina Belotcerkovskaya, Pavel Davidovich, Sylvia Sura-Trueba, Alexander V Garabadzhiu, Seamus J Martin
Sterile inflammation is initiated by molecules released from necrotic cells, called damage-associated molecular patterns (DAMPs). Members of the extended IL-1 cytokine family are important DAMPs, are typically only released through necrosis, and require limited proteolytic processing for activation. The IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, are expressed as inactive precursors and have been implicated as key initiators of psoriatic-type skin inflammation. We have recently found that IL-36 family cytokines are proteolytically processed and activated by the neutrophil granule-derived proteases, elastase, and cathepsin G...
March 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29474749/mek-erk-signaling-diametrically-controls-the-stimulation-of-il-23p19-and-ebi3-expression-in-epithelial-cells-by-il-36%C3%AE
#19
Glen M Scholz, Jacqueline E Heath, Katrina A Walsh, Eric C Reynolds
Interleukin (IL)-36 cytokines are important regulators of mucosal homeostasis and inflammation. We previously established that oral epithelial cells strongly upregulate IL-36γ expression in response to the bacterial pathogen Porphyromonas gingivalis. Here, we have established that IL-36γ stimulates the expression of the IL-12 cytokine family members, IL-23p19 and Epstein-Barr Virus-Induced Gene 3 (EBI3), by oral epithelial cells; their expression was also selectively stimulated by IL-36α. Notably, IL-23p19 and EBI3 expression was not stimulated by P...
February 23, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29434599/rna-seq-analysis-of-il-1b-and-il-36-responses-in-epidermal-keratinocytes-identifies-a-shared-myd88-dependent-gene-signature
#20
William R Swindell, Maria A Beamer, Mrinal K Sarkar, Shannon Loftus, Joseph Fullmer, Xianying Xing, Nicole L Ward, Lam C Tsoi, Michelle J Kahlenberg, Yun Liang, Johann E Gudjonsson
IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). This study used RNA-seq to profile the transcriptome of primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B, or IL-36G. We identified some early IL-1B-specific responses (8 h posttreatment), but nearly all late IL-1B responses were replicated by IL-36 cytokines (24 h posttreatment). Type I and II interferon genes exhibited time-dependent response patterns, with early induction (8 h) followed by no response or repression (24 h)...
2018: Frontiers in Immunology
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