Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Analysis of gene expression in human Bronchial Alveolar Lavage Cell (BAL) cell pellets

ABSTRACT: Clinical subphenotypes of asthma are characterized by pathological, cellular, and molecular heterogeneity of the airway. Gene expression profiling of airway inflammatory cells in diseased patients by microarray analysis will provide insight into the molecular heterogeneity and support the development of hypotheses of pathological mechanisms. Moderate asthmatic patients and healthy controls were participants in the Study of the Mechanisms of Asthma (MAST, clinicaltrials.gov: NCT00595153). Severe asthmatic patients were participants in the BOBCAT study (as described in Jia G JACI 2012 and Arron JR ERJ 2014). RNA (Qiagen AllPrep with on-column DNase treatment) was isolated from Bronchial Alveolar Lavage cells for gene expression microarray analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Mark McCreary

PROVIDER: E-GEOD-74986 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response.

Sun Yonglian Y Peng Ivan I Webster Joshua D JD Suto Eric E Lesch Justin J Wu Xiumin X Senger Kate K Francis George G Barrett Kathy K Collier Jenna L JL Burch Jason D JD Zhou Meijuan M Chen Yuan Y Chan Connie C Eastham-Anderson Jeff J Ngu Hai H Li Olga O Staton Tracy T Havnar Charles C Jaochico Allan A Jackman Janet J Jeet Surinder S Riol-Blanco Lorena L Wu Lawren C LC Choy David F DF Arron Joseph R JR McKenzie Brent S BS Ghilardi Nico N Ismaili Moulay Hicham Alaoui MH Pei Zhonghua Z DeVoss Jason J Austin Cary D CD Lee Wyne P WP Zarrin Ali A AA

Science signaling 20151201 405

Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and decreased amounts of TH2-type cytokines in the bronchoalveolar lavage fluid. We found that a small-molecule selective inhibitor of ITK blocked TCR-mediated signaling in cultured TH2 ce ...[more]

PMID: 26628680

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Project description:Rationale: Asthma and atopy shares common features including Th2-inflammation. However, impairment of airway function seems to be absent in atopy. Increased understanding of the complex cellular and molecular pathways defining the similarities and differences between asthma and atopy may be achieved by transcriptomic analysis (RNA-Seq). Hypothesis and Aims: As the airway smooth muscle (ASM) layer plays an important role in airway function, we hypothesized that the transcriptomic profile of the ASM layer in endobronchial biopsies is different between atopic asthma patients and atopic healthy controls. First, we examined the differences in transcriptomic profiles of the ASM layer in endobronchial biopsies between atopic mild, steroid-free asthma patients, and atopic and non-atopic healthy controls. Second, we investigated the association between the transcriptomic profiles of the ASM layer and airway function. Methods: This cross-sectional study included 12 steroid-free atopic asthma patients, 6 atopic, and 6 non-atopic healthy controls. RNA of ASM from 4 endobronchial biopsies per subject was isolated and sequenced (GS FLX+, 454/Roche). Ingenuity Pathway Analysis was used to identify gene networks. Comparison of the numbers of reads per gene in asthma and controls was based on the negative binomial distribution. At the current sample size the estimated false discovery rate was approximately 1%. Results: Yield of isolated RNA was 30-821ng. We identified 174 differentially expressed genes between asthma and atopic controls, 108 between asthma and non-atopic controls, and 135 between atopic and non-atopic controls. A set of 8 genes was identified, which seems to define asthma patients from non-asthmatic controls regardless of atopy. Four of these genes were significantly associated with airway hyperresponsiveness. Conclusion: A difference in transcriptomic profile of the airway smooth muscle layer in asthma patients compared to atopic and non-atopic healthy controls may lead to a different regulation of inflammatory pathways and of airway smooth muscle function and development resulting in impaired airway function. This cross-sectional transcriptomics study consisted of 2 visits. At visit 1, asthma patients (n=12), and healthy atopic (n=6) and non-atopic (n=6) controls were screened for eligibility to participate according to the in- and exclusion criteria. Spirometry and a methacholine bronchoprovocation test were performed. At visit 2, FEV1 reversibility was measured and 4 endobronchial biopsies per subject were collected during a bronchoscopy. Airway smooth muscle was collected from the biopsies by laser capture microdissection and total RNA isolated. cDNA was prepared using the Ovation RNA-Seq System (NuGEN). RNA-Seq was performed using the GS FLX+ instrument (454/Roche). Sequence reads were mapped against the human genome (hg19; UCSC). Comparison of the numbers of reads per gene between asthma and healthy controls was based on the negative binomial distribution and carried out with the R package DESeq including correction for multiple testing.

Dataset Information

Analysis of gene expression in human Bronchial Alveolar Lavage Cell (BAL) cell pellets

Publications

Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response.

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