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Ormdl3

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https://www.readbyqxmd.com/read/28333149/upregulation-of-mir-665-promotes-apoptosis-and-colitis-in-inflammatory-bowel-disease-by-repressing-the-endoplasmic-reticulum-stress-components-xbp1-and-ormdl3
#1
Manying Li, Shenghong Zhang, Yun Qiu, Yao He, Baili Chen, Ren Mao, Yi Cui, Zhirong Zeng, Minhu Chen
MicroRNAs are critical post-transcriptional regulators of gene expression and key mediators of pathophysiology of inflammatory bowel disease (IBD). This study is aimed to study the role of miR-665 in the progression of IBD. Real-time PCR analysis was used to determine miR-665 expression in 89 freshly isolated IBD samples and dextran sulfate sodium (DSS)-induced colonic mucosal tissues. The role of miR-665 in inducing apoptosis and colitis were examined by Annexin V, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, colony formation in vitro and DSS-induced colitis mice model in vivo...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28275141/cutting-edge-targeting-epithelial-ormdl3-increases-rather-than-reduces-airway-responsiveness-and-is-associated-with-increased-sphingosine-1-phosphate
#2
Marina Miller, Arvin B Tam, James L Mueller, Peter Rosenthal, Andrew Beppu, Ruth Gordillo, Matthew D McGeough, Christine Vuong, Taylor A Doherty, Hal M Hoffman, Maho Niwa, David H Broide
In this study, we used cre-lox techniques to generate mice selectively deficient in ORMDL3 in airway epithelium (Ormdl3(Δ2-3/Δ2-3)/CC10) to simulate an inhaled therapy that effectively inhibited ORMDL3 expression in the airway. In contrast to the anticipated reduction in airway hyperresponsiveness (AHR), OVA allergen-challenged Ormdl3(Δ2-3/Δ2-3)/CC10 mice had a significant increase in AHR compared with wild-type mice. Levels of airway inflammation, mucus, fibrosis, and airway smooth muscle were no different in Ormdl3(Δ2-3/Δ2-3)/CC10 and wild-type mice...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28241063/role-of-dna-methylation-in-expression-control-of-the-ikzf3-gsdma-region-in-human-epithelial-cells
#3
Sanny Moussette, Abeer Al Tuwaijri, Hamid-Reza Kohan-Ghadr, Samar Elzein, Raquel Farias, Julie Bérubé, Bianca Ho, Catherine Laprise, Cynthia G Goodyer, Simon Rousseau, Anna K Naumova
Chromosomal region 17q12-q21 is associated with asthma and harbors regulatory polymorphisms that influence expression levels of all five protein-coding genes in the region: IKAROS family zinc finger 3 (Aiolos) (IKZF3), zona pellucida binding protein 2 (ZPBP2), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and gasdermins A and B (GSDMA, GSDMB). Furthermore, DNA methylation in this region has been implicated as a potential modifier of the genetic risk of asthma development. To further characterize the effect of DNA methylation, we examined the impact of treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) that causes DNA demethylation, on expression and promoter methylation of the five 17q12-q21 genes in the human airway epithelium cell line NuLi-1, embryonic kidney epithelium cell line 293T and human adenocarcinoma cell line MCF-7...
2017: PloS One
https://www.readbyqxmd.com/read/28192616/association-of-ormdl3-with-rhinovirus-induced-endoplasmic-reticulum-stress-and-type-i-interferon-responses-in-human-leukocytes
#4
Yi-Ping Liu, Victoria Rajamanikham, Marissa Baron, Sagar Patel, Sameer K Mathur, Elizabeth A Schwantes, Carole Ober, Daniel J Jackson, James E Gern, Robert F Lemanske, Judith A Smith
BACKGROUND: Children with risk alleles at the 17q21 genetic locus who wheeze during rhinovirus illnesses have a greatly increased likelihood of developing childhood asthma. In mice, overexpression of the 17q21 gene ORMDL3 leads to airway remodeling and hyper-responsiveness. However, the mechanisms by which ORMDL3 predisposes to asthma are unclear. Previous studies have suggested that ORMDL3 induces endoplasmic reticulum (ER) stress and production of the type I interferon (IFN) regulated chemokine CXCL10...
February 13, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28031110/-recombinant-platanus-pollen-allergen-2-rpla-a2-up-regulates-the-expression-of-ormdl3-mediated-by-gata3-in-nih3t3-cells
#5
Huiwen Zhang, Lili Zhuang, Rui Jin, Nannan Li, Guoping Zhou
Objective To identify the effect and mechanism of recombinant platanus pollen allergen 2 (rPla a2) on the transcription and expression of orosomucoid 1-like 3 (ORMDL3) gene in NIH3T3 cells. Methods Quantitative real-time PCR and Western blot analysis were used to detect the influence of rPla a2 on the mRNA and protein levels of ORMDL3 and GATA3. After transfection of GATA3 siRNA or pcDNA-GATA3, the role of GATA3 was evaluated in rPla a2 regulating ORMDL3 expression. Dual-luciferase reporter assay was performed to measure the influence of rPla a2 and GATA3 on ORMDL3 promoter activity...
January 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28030368/sphingolipids-ormdl3-and-asthma-what-is-the-evidence
#6
Tilla S Worgall
PURPOSE OF REVIEW: Genome-wide association studies identified ORMDL3, a protein of the endoplasmic reticulum, as a significant asthma risk factor. ORMDL3 is one of three ORMDL proteins that integrate multiple signals to maintain sphingolipid homeostasis. Studies that investigated potential mechanisms for how increased ORMDL3 might affect asthma are summarized. RECENT FINDINGS: Investigations focused on decreased sphingolipid synthesis and on the unfolded protein response because ORMDL3 had been implicated in both...
March 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27932194/associations-between-nod2-irgm-and-ormdl3-polymorphisms-and-pediatric-onset-inflammatory-bowel-disease-in-the-lithuanian-population
#7
Gitana Pranculienė, Rūta Steponaitienė, Jurgita Skiecevičienė, Rūta Kučinskienė, Gediminas Kiudelis, Kęstutis Adamonis, Liutauras Labanauskas, Limas Kupčinskas
BACKGROUND AND OBJECTIVE: Recent GWAS and meta-analyses have revealed about 200 susceptibility genes/loci for inflammatory bowel diseases (IBD). However, only a small number of studies were performed in early-onset IBD. The aim of this study was to assess the association between NOD2, IL23R, ATG16L1, IRGM, IL10, NKX2-3 and ORMDL3 variants and early-onset IBD. MATERIALS AND METHODS: A total of 76 affected individuals (30 with Crohn's disease [CD] and 46 with ulcerative colitis [UC]) at the age of ≤17 years and 158 matched controls recruited in Lithuania were genotyped for the known genetic susceptibility variants in NOD2 (Arg702Trp (rs2066844), Gly908Arg (rs2066845) and Leu1007insC (rs2066847)), IL23R (rs11209026), ATG16L1 (rs2241880), IRGM (rs4958847), IL10 (rs3024505), NKX2-3 (rs11190140) and ORMDL3 (rs2872507) genes...
2016: Medicina
https://www.readbyqxmd.com/read/27895690/rhinovirus-and-childhood-asthma-an-update
#8
REVIEW
Dae Jin Song
Asthma is recognized as a complex disease resulting from interactions between multiple genetic and environmental factors. Accumulating evidence suggests that respiratory viral infections in early life constitute a major environmental risk factor for the development of childhood asthma. Respiratory viral infections have also been recognized as the most common cause of asthma exacerbation. The advent of molecular diagnostics to detect respiratory viruses has provided new insights into the role of human rhinovirus (HRV) infections in the pathogenesis of asthma...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/27848966/17q21-asthma-risk-variants-switch-ctcf-binding-and-regulate-il-2-production-by-t-cells
#9
Benjamin Joachim Schmiedel, Grégory Seumois, Daniela Samaniego-Castruita, Justin Cayford, Veronique Schulten, Lukas Chavez, Ferhat Ay, Alessandro Sette, Bjoern Peters, Pandurangan Vijayanand
Asthma and autoimmune disease susceptibility has been strongly linked to genetic variants in the 17q21 haploblock that alter the expression of ORMDL3; however, the molecular mechanisms by which these variants perturb gene expression and the cell types in which this effect is most prominent are unclear. We found several 17q21 variants overlapped enhancers present mainly in primary immune cell types. CD4(+) T cells showed the greatest increase (threefold) in ORMDL3 expression in individuals carrying the asthma-risk alleles, where ORMDL3 negatively regulated interleukin-2 production...
November 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27835674/lymphocyte-activation-dynamics-is-shaped-by-hereditary-components-at-chromosome-region-17q12-q21
#10
Amado Carreras-Sureda, Fanny Rubio-Moscardo, Alex Olvera, Jordi Argilaguet, Kerstin Kiefer, Beatriz Mothe, Andreas Meyerhans, Christian Brander, Rubén Vicente
Single nucleotide polymorphisms (SNPs) located in the chromosome region 17q12-q21 are risk factors for asthma. Particularly, there are cis-regulatory haplotypes within this region that regulate differentially the expression levels of ORMDL3, GSDMB and ZPBP2 genes. Remarkably, ORMDL3 has been shown to modulate lymphocyte activation parameters in a heterologous expression system. In this context, it has been shown that Th2 and Th17 cytokine production is affected by SNPs in this region. Therefore, we aim to assess the impact of hereditary components within region 17q12-q21 on the activation profile of human T lymphocytes, focusing on the haplotype formed by allelic variants of SNPs rs7216389 and rs12936231...
2016: PloS One
https://www.readbyqxmd.com/read/27826095/oroscomucoid-like-protein-3-ormdl3-transgenic-mice-have-reduced-levels-of-sphingolipids-including-sphingosine-1-phosphate-and-ceramide
#11
Marina Miller, Peter Rosenthal, Andrew Beppu, Ruth Gordillo, David H Broide
No abstract text is available yet for this article.
November 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27784618/benomyl-induced-effects-of-ormdl3-overexpression-via-oxidative-stress-in-human-bronchial-epithelial-cells
#12
Yoonjeong Jang, Ah Young Lee, Ji-Eun Kim, Sang-Hee Jeong, Jun Sung Kim, Myung-Haing Cho
The respiratory system is a major site of exposure route during pesticide use. Although pesticide exposure is associated with chronic respiratory diseases including asthma, the underlying pathophysiological mechanism remains to be elucidated. In this study, we investigated the in vitro effects of benomyl-induced ORMDL3 overexpression on the toxicological mechanism using the human bronchial epithelial cell line 16HBE14o-. Benomyl increased reactive oxygen species and Ca(2+) levels, and asthma-related ADAM33 and ORMDL3 expression in 16HBE14o- cells...
December 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27660012/gu-ben-fang-xiao-decoction-attenuates-sustained-airway-inflammation-by-suppressing-er-stress-response-in-a-murine-asthma-remission-model-of-respiratory-syncytial-virus-infection
#13
Yuan Lu, Jian-Ya Xu, Xiao-Hua Zhang, Xia Zhao
ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous...
November 4, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27658857/the-genetic-and-epigenetic-landscapes-of-the-epithelium-in-asthma
#14
Fatemeh Moheimani, Alan C-Y Hsu, Andrew T Reid, Teresa Williams, Anthony Kicic, Stephen M Stick, Philip M Hansbro, Peter A B Wark, Darryl A Knight
Asthma is a global health problem with increasing prevalence. The airway epithelium is the initial barrier against inhaled noxious agents or aeroallergens. In asthma, the airway epithelium suffers from structural and functional abnormalities and as such, is more susceptible to normally innocuous environmental stimuli. The epithelial structural and functional impairments are now recognised as a significant contributing factor to asthma pathogenesis. Both genetic and environmental risk factors play important roles in the development of asthma with an increasing number of genes associated with asthma susceptibility being expressed in airway epithelium...
2016: Respiratory Research
https://www.readbyqxmd.com/read/27645259/ormdl3-expression-levels-have-no-influence-on-the-activity-of-serine-palmitoyltransferase
#15
Assem Zhakupova, Nincy Debeuf, Michiel Krols, Wendy Toussaint, Leen Vanhoutte, Irina Alecu, Zoltán Kutalik, Peter Vollenweider, Daniela Ernst, Arnold von Eckardstein, Bart N Lambrecht, Sophie Janssens, Thorsten Hornemann
ORMDL proteins are believed to be negative regulators of serine palmitoyltransferase (SPT), which catalyzes the first and rate limiting step in sphingolipid (SL) de novo synthesis. Several single-nucleotide polymorphisms (SNPs) that are close to the ORMDL3 locus have been reported to increase ORMDL3 expression and to be associated with an elevated risk for early childhood asthma; however, the direct effect of ORMDL3 expression on SPT activity and its link to asthma remains elusive. In this study, we investigated whether ORMDL3 expression is associated with changes in SPT activity and total SL levels...
December 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27623174/pulmonary-ormdl3-is-critical-for-induction-of-alternaria-induced-allergic-airways-disease
#16
Stephan Löser, Lisa G Gregory, Youming Zhang, Katrein Schaefer, Simone A Walker, James Buckley, Laura Denney, Charlotte H Dean, William O C Cookson, Miriam F Moffatt, Clare M Lloyd
BACKGROUND: Genome-wide association studies have identified the ORM (yeast)-like protein isoform 3 (ORMDL3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma. OBJECTIVE: We sought to investigate in vivo the functional role of ORMDL3 in disease inception. METHODS: An Ormdl3-deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata was determined...
September 10, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27497278/advances-in-asthma-2015-across-the-lifespan
#17
Andrew H Liu, William C Anderson, Cullen M Dutmer, Daniel A Searing, Stanley J Szefler
In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened...
August 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27313060/ormdl-proteins-regulate-ceramide-levels-during-sterile-inflammation
#18
Lin Cai, Clement Oyeniran, Debolina D Biswas, Jeremy Allegood, Sheldon Milstien, Tomasz Kordula, Michael Maceyka, Sarah Spiegel
The bioactive sphingolipid metabolite, ceramide, regulates physiological processes important for inflammation and elevated levels of ceramide have been implicated in IL-1-mediated events. Although much has been learned about ceramide generation by activation of sphingomyelinases in response to IL-1, the contribution of the de novo pathway is not completely understood. Because yeast ORM1 and ORM2 proteins negatively regulate ceramide levels through inhibition of serine palmitoyltransferase, the first committed step in ceramide biosynthesis, we examined the functions of individual mammalian ORM orthologs, ORM (yeast)-like (ORMDL)1-3, in regulation of ceramide levels...
August 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27163155/polymorphisms-and-haplotypes-of-the-chromosome-locus-17q12-17q21-1-contribute-to-adult-asthma-susceptibility-in-slovenian-patients
#19
Mateja Žavbi, Peter Korošec, Matjaž Fležar, Sabina Škrgat Kristan, Mateja Marc Malovrh, Matija Rijavec
One of the major asthma susceptibility loci is 17q12-17q21.1, but the relationship between this locus and adult asthma is unclear. Association analysis of 13 single nucleotide polymorphisms (SNPs) and haplotypes from 17q12-17q21.1 was performed in 418 adult patients with asthma and 288 controls from Slovenia. Single SNP analysis revealed only marginal associations with adult asthma for SNPs located in GSDMA, GSDMB, ORMDL3 and ZPBP2 genes, and rs7219080 was the most highly associated. Analyses of asthma phenotypes found no association with atopy or lung function, but rs2305480 and rs8066582 were associated with childhood asthma and rs9916279 was associated with asthma in smokers...
June 2016: Human Immunology
https://www.readbyqxmd.com/read/27130253/molecular-modulators-of-store-operated-calcium-entry
#20
REVIEW
Jose J Lopez, Letizia Albarran, Luis J Gómez, Tarik Smani, Gines M Salido, Juan A Rosado
Three decades ago, store-operated Ca(2+) entry (SOCE) was identified as a unique mechanism for Ca(2+) entry through plasma membrane (PM) Ca(2+)-permeable channels modulated by the intracellular Ca(2+) stores, mainly the endoplasmic reticulum (ER). Extensive analysis of the communication between the ER and the PM leads to the identification of the protein STIM1 as the ER-Ca(2+) sensor that gates the Ca(2+) channels in the PM. Further analysis on the biophysical, electrophysiological and biochemical properties of STIM1-dependent Ca(2+) channels has revealed the presence of a highly Ca(2+)-selective channel termed Ca(2+) release-activated Ca(2+) channel (CRAC), consisting of Orai1 subunits, and non-selective cation channels named store-operated channels (SOC), including both Orai1 and TRPC channel subunits...
August 2016: Biochimica et Biophysica Acta
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