Tag: Expression

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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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Expression of adenosine receptors in monocytes from patients with bronchial asthma.

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Expression of adenosine receptors in monocytes from patients with bronchial asthma.

Biochem Biophys Res Commun. 2015 Jul 29;

Authors: Yuryeva K, Saltykova I, Ogorodova L, Kirillova N, Kulikov E, Korotkaya E, Iakovleva Y, Feoktistov I, Sazonov A, Ryzhov S

Abstract
Adenosine is generated from adenosine triphosphate, which is released by stressed and damaged cells. Adenosine levels are significantly increased in patients with bronchial asthma (BA) and mediate mast cell degranulation and bronchoconstriction. Over the last decade, increasing evidence has shown that adenosine can modulate the innate immune response during monocytes differentiation towards mature myeloid cells. These adenosine-differentiated myeloid cells, characterized by co-expression of monocytes/macrophages and dendritic cell markers such as CD14 and CD209, produce high levels of pro-inflammatory cytokines, thus contributing to the pathogenesis of BA and chronic obstructive pulmonary disease. We found that expression of ADORA2A and ADORA2B are increased in monocytes obtained from patients with BA, and are associated with the generation of CD14(pos)CD209(pos) pro-inflammatory cells. A positive correlation between expression of ADORA2B and IL-6 was identified in human monocytes and may explain the increased expression of IL-6 mRNA in asthmatics. Taken together, our results suggest that monocyte-specific expression of A2 adenosine receptors plays an important role in pro-inflammatory activation of human monocytes, thus contributing to the progression of asthma.

PMID: 26232643 [PubMed – as supplied by publisher]

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Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles.

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Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles.

J Allergy Clin Immunol. 2015 Apr 9;

Authors: Persson H, Kwon AT, Ramilowski JA, Silberberg G, Söderhäll C, Orsmark-Pietras C, Nordlund B, Konradsen JR, de Hoon MJ, Melén E, Hayashizaki Y, Hedlin G, Kere J, Daub CO

Abstract
BACKGROUND: Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA).
OBJECTIVE: We sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes.
METHODS: Gene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs.
RESULTS: Sample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA), which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA.
CONCLUSION: Circulating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.

PMID: 25863981 [PubMed – as supplied by publisher]

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Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex vivo/in vitro exposure study in respiratory disease patients.

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Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex vivo/in vitro exposure study in respiratory disease patients.

Mutagenesis. 2014 Nov 6;

Authors: Kumar A, Najafzadeh M, Jacob BK, Dhawan A, Anderson D

Abstract
Zinc oxide (ZnO) nanoparticles are the mostly used engineered metal oxide nanoparticles in consumer products. This has increased the likelihood of human exposure to this engineered nanoparticle (ENPs) through different routes. At present, the majority of the studies concerning ZnO ENPs toxicity have been conducted using in vitro and in vivo systems. In this study, for the first time we assessed the effect of ZnO ENPs on the major cellular pathways in the lymphocytes of healthy individuals as well as in susceptible patients suffering from lung cancer, chronic obstructive pulmonary disease (COPD) and asthma. Using the differential expression analysis, we observed a significant (P < 0.05) dose-dependent (10, 20 and 40 µg/ml for 6h) increase in the expression of tumour suppressor protein p53 (40, 60 and 110%); Ras p21 (30, 52 and 80%); c-Jun N-terminal kinases; JNKs) (28, 47 and 78%) in lung cancer patient samples treated with ZnO ENPs compared to healthy controls. A similar trend was also seen in COPD patient samples where a significant (P < 0.05) dose-dependent increase in the expression of tumour suppressor protein p53 (26, 45 and 84%), Ras p21 (21, 40 and 77%), JNKs (17, 32 and 69%) was observed after 6h of ZnO ENPs treatment at the aforesaid concentrations. However, the increase in the expression profile of tested protein was not significant in the asthma patients as compared to controls. Our results reiterate the concern about the safety of ZnO ENPs in consumer products and suggest the need for a complete risk assessment of any new ENPs before its use.

PMID: 25381309 [PubMed – as supplied by publisher]

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Study to Examine the Cytokine Levels, Gene Expression and Safety of a Single Nasal Dose of JNJ-43260295, in Healthy Participants, and Atopic Participants With Mild to Mild-Persistent Asthma

Conditions:   Healthy;   Asthma
Interventions:   Drug: JNJ-43260295;   Drug: Placebo;   Other: Nasal Allergen Challenge
Sponsor:   Janssen Research & Development, LLC
Not yet recruiting – verified September 2014

View full post on ClinicalTrials.gov: asthma | received in the last 14 days