Decreased Epithelial and Plasma miR-181b-5p Expression Associates with Airway Eosinophilic Inflammation in Asthma.

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Decreased Epithelial and Plasma miR-181b-5p Expression Associates with Airway Eosinophilic Inflammation in Asthma.

Clin Exp Allergy. 2016 May 18;

Authors: Huo X, Zhang K, Yi L, Mo Y, Liang Y, Zhao J, Zhang Z, Xu Y, Zhen G

Abstract
BACKGROUND: Airway eosinophilic inflammation is a pivotal feature of asthma. Epithelial cells play critical roles in airway eosinophilia. We hypothesized that epithelial microRNAs (miRNAs) are involved in airway eosinophilia.
OBJECTIVE: This study investigated the associations between epithelial and plasma miR-181b-5p and airway eosinophilic inflammation, and the possible mechanism by which miR-181b-5p participates in eosinophilic inflammation.
METHODS: Epithelial miRNAs expression was profiled by miRNA array in 8 subjects with asthma and 4 healthy controls. Epithelial miR-181b-5p expression was confirmed by quantitative PCR in the subjects for array experiment and another cohort including 21 subjects with asthma and 10 controls. Plasma miR-181b-5p was determined by quantitative PCR in 72 subjects with asthma and 35 controls. Correlation assays between epithelial or plasma miR-181b-5p expression and airway eosinophilia were performed. The target of miR-181b-5p, SPP1, was predicted by online algorithms and verified in BEAS-2B cells. The role of miR-181b-5p in epithelial proinflammatory cytokine expression was examined in an in vitro system.
RESULTS: Epithelial miR-181b-5p expression was decreased in subjects with asthma. Epithelial miR-181b-5p levels were inversely correlated with sputum and bronchial submucosal eosinophilia. Plasma miR-181b-5p was decreased and correlated with epithelial miR-181b-5p in subjects with asthma. There was a strong inverse correlation between plasma miR-181b-5p and airway eosinophilia in subjects with asthma. Plasma miR-181b-5p was increased after inhaled corticosteroids treatment. We verified that SPP1 is a target of miR-181b-5p. In human bronchial epithelial cells, miR-181b-5p regulated IL-13-induced IL-1? and CCL11 expression by targeting SPP1. Dexamethasone restored IL-13-induced miR-181b-5p downregulation and suppressed IL-13-induced SPP1, IL-1? and CCL11 expression.
CONCLUSIONS AND CLINICAL RELEVANCE: Epithelial and plasma miR-181b-5p are potential biomarkers for airway eosinophilia in asthma. MiR-181b-5p may participate in eosinophilic airway inflammation by regulating proinflammatory cytokines expression via targeting SPP1. This article is protected by copyright. All rights reserved.

PMID: 27192552 [PubMed – as supplied by publisher]

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Dr. Robert Nathan from Asthma and Allergy Associates Invited to Speak in … – PR Web (press release)

Dr. Robert Nathan from Asthma and Allergy Associates Invited to Speak in
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Asthma and Allergy Associates' Dr. Robert Nathan speeches regarding asthma treatments research and the manuscript for Dulera 100/5 used for FDA approval attracts international attention. Share on Twitter Share on Facebook Share on Google+ Share on 

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A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk.

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A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk.

Genes Immun. 2013 Aug 15;

Authors: Revez JA, Bain L, Chapman B, Powell JE, Jansen R, Duffy DL, Tung JY, AAGC Collaborators, Matheson MC, Marks GB, Hui J, Le Souëf P, Danoy P, Baltic S, Nyholt DR, Jenkins M, Hayden C, Beilby J, Cheah F, Madden PA, Heath AC, Hopper JL, Musk B, Leeder SR, Walters EH, James A, Jones G, Abramson MJ, Robertson CF, Dharmage SC, Brown MA, Thompson PJ, Penninx BW, Visscher PM, De Geus EJ, Boomsma DI, Hinds DA, Martin NG, Montgomery GW, Ferreira MA

Abstract
The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ?20?ng?ml(-1) and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4?ng?ml(-1). Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16?705 asthmatics and 30?809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.Genes and Immunity advance online publication, 15 August 2013; doi:10.1038/gene.2013.38.

PMID: 23945879 [PubMed – as supplied by publisher]

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