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https://www.readbyqxmd.com/read/27895690/rhinovirus-and-childhood-asthma-an-update
#1
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
#2
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
#3
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
#4
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
#5
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...
October 23, 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
#6
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
#7
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
#8
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
#9
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 ORMDL3 (ORM (yeast)-like protein isoform 3) 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 determined...
September 10, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27497278/advances-in-asthma-2015-across-the-lifespan
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27097577/-ormdl3-polymorphisms-and-their-relationship-with-opn-and-tgf-%C3%AE-1-levels-in-children-with-asthma-in-hunan-china-an-analysis-of-98-cases
#14
Ai-Mei Yang, Rong Huang, Shi-Jie Jin
OBJECTIVE: To investigate ORMDL3 polymorphisms in children with asthma in Hunan, China, and to determine the relationship between ORMDL3 polymorphisms and serum osteopontin (OPN) and transforming growth factor-β1 (TGF-β1) levels. METHODS: Peripheral blood samples were collected in children with asthma (n=98; astma group) or without asthma (n=30; control group) from Hunan, China. The asthma group was subdivided into atopic (n=62) and non-atopic (n=36) subgroups...
April 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/26969910/the-role-of-ormdl-proteins-guardians-of-cellular-sphingolipids-in-asthma
#15
REVIEW
T Paulenda, P Draber
A family of widely expressed ORM-like (ORMDL) proteins has been recently linked to asthma in genomewide association studies in humans and extensively explored in in vivo studies in mice. ORMDL proteins are key regulators of serine palmitoyltransferase, an enzyme catalyzing the initial step of sphingolipid biosynthesis. Sphingolipids play prominent roles in cell signaling and response to stress, and they affect the mechanistic properties of cellular membranes. Deregulation of sphingolipid biosynthesis and their recycling has been proven to support and even cause several diseases including allergy, inflammation, and asthma...
July 2016: Allergy
https://www.readbyqxmd.com/read/26946626/effect-of-gubenfangxiao-decoction-on-respiratory-syncytial-virus-induced-asthma-and-expression-of-asthma-susceptibility-gene-orosomucoid-1-like-protein-3-in-mice
#16
Zhengguang Huang, Lijuan Gao, Xia Zhao, Hao Ling, Wenjun Chen
OBJECTIVE: To investigate the effect of Guben-fangxiao decoction (GBFXD) on respiratory-syncytial-virus (RSV)-induced asthma and the expression of asthma susceptibility gene, orosomucoid 1-like protein 3 (ORMDL3) in mice. METHODS: Seventy-two female BALB/c mice were randomly assigned to normal, model, GBFXD high dose, GBFXD moderate dose, GBFXD low dose and montelukast groups. An asthma model was induced via intraperitoneal injection and aerosol inhalation of ovalbumin (OVA) and repeated intranasal instillation of RSV in all mice, except those in the normal group...
February 2016: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
https://www.readbyqxmd.com/read/26836624/rhinovirus-induced-asthma-exacerbations-and-risk-populations
#17
Laura Coleman, Ingrid A Laing, Anthony Bosco
PURPOSE OF REVIEW: This article discusses recent findings into the mechanisms that determine how viruses trigger asthma exacerbations. RECENT FINDINGS: Substantial progress has been made in our understanding of the pathogenesis of virus-induced asthma exacerbations. This includes new insights into the role of bacteria, the regulation of interferon responses, and the discovery of innate immune pathways that link viral infections with allergic inflammation. Progress has also been made in elucidating the genetic risk factors for asthma exacerbations, most notably the contribution of the ORMDL3/GSDMB locus on 17q, the mechanisms underlying the farming effect, and the discovery that CDHR3 binds to rhinovirus species C...
April 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/26637347/airway-reactivity-and-sphingolipids-implications-for-childhood-asthma
#18
Jennie G Ono, Tilla S Worgall, Stefan Worgall
Asthma is a clinically heterogeneous disorder, whose onset and progression results from a complex interplay between genetic susceptibility, allergens, and viral triggers. Sphingolipids and altered sphingolipid metabolism have emerged as potential key contributors to the pathogenesis of asthma. Orosomucoid-like 3 gene (ORMDL3) and the asthma susceptibility locus 17q21 have been strongly and reproducibly linked to childhood asthma, but how this gene is functionally linked to asthma is incompletely understood...
December 2015: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/26603569/ormdl3-contributes-to-the-risk-of-atherosclerosis-in-chinese-han-population-and-mediates-oxidized-low-density-lipoprotein-induced-autophagy-in-endothelial-cells
#19
Xiaochun Ma, Rongfang Qiu, Jie Dang, Jiangxia Li, Qin Hu, Shan Shan, Qian Xin, Wenying Pan, Xianli Bian, Qianqian Yuan, Feng Long, Na Liu, Yan Li, Fei Gao, Chengwei Zou, Yaoqin Gong, Qiji Liu
ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) is a universally confirmed susceptibility gene for asthma and has recently emerged as a crucial modulator in lipid metabolism, inflammation and endoplasmic reticulum (ER) stress-the mechanisms also closely involved in atherosclerosis (AS). Here we first presented the evidence of two single nucleotide polymorphisms regulating ORMDL3 expression (rs7216389 and rs9303277) significantly associated with AS risk and the evidence of increased ORMDL3 expression in AS cases compared to controls, in Chinese Han population...
November 25, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26407610/negative-regulatory-roles-of-ormdl3-in-the-fc%C3%AE%C2%B5ri-triggered-expression-of-proinflammatory-mediators-and-chemotactic-response-in-murine-mast-cells
#20
Viktor Bugajev, Ivana Halova, Lubica Draberova, Monika Bambouskova, Lucie Potuckova, Helena Draberova, Tomas Paulenda, Sergi Junyent, Petr Draber
Single-nucleotide polymorphism studies have linked the chromosome 17q12-q21 region, where the human orosomucoid-like (ORMDL)3 gene is localized, to the risk of asthma and several other inflammatory diseases. Although mast cells are involved in the development of these diseases, the contribution of ORMDL3 to the mast cell physiology is unknown. In this study, we examined the role of ORMDL3 in antigen-induced activation of murine mast cells with reduced or enhanced ORMDL3 expression. Our data show that in antigen-activated mast cells, reduced expression of the ORMDL3 protein had no effect on degranulation and calcium response, but significantly enhanced phosphorylation of AKT kinase at Ser 473 followed by enhanced phosphorylation and degradation of IκBα and translocation of the NF-κB p65 subunit into the nucleus...
March 2016: Cellular and Molecular Life Sciences: CMLS
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