Journal article
Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis
The European respiratory journal, Vol.47(6), pp.1797-1808
06/2016
DOI: 10.1183/13993003.01469-2015
PMCID: PMC5134922
PMID: 27103383
Abstract
A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)-STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine-cytokine receptor interactions, and Toll-like receptor, chemokine and JAK-STAT signalling pathways.We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways.
Details
- Title: Subtitle
- Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis
- Creators
- Li Li - Dept of Medicine, National Jewish Health, Denver, CO, USA Division of Pulmonary and Critical Care Sciences, Dept of Medicine, School of Medicine, Denver, CO, USA lil@njhealth.orgLori J Silveira - Dept of Medicine, National Jewish Health, Denver, CO, USANabeel Hamzeh - Dept of Medicine, National Jewish Health, Denver, CO, USA Division of Pulmonary and Critical Care Sciences, Dept of Medicine, School of Medicine, Denver, CO, USAMay Gillespie - Dept of Medicine, National Jewish Health, Denver, CO, USAPeggy M Mroz - Dept of Medicine, National Jewish Health, Denver, CO, USAAnnyce S Mayer - Dept of Medicine, National Jewish Health, Denver, CO, USA Division of Pulmonary and Critical Care Sciences, Dept of Medicine, School of Medicine, Denver, CO, USA Environmental Occupational Health Dept, School of Public Health, University of Colorado, Denver, CO, USATasha E Fingerlin - Dept of Medicine, National Jewish Health, Denver, CO, USALisa A Maier - Dept of Medicine, National Jewish Health, Denver, CO, USA Division of Pulmonary and Critical Care Sciences, Dept of Medicine, School of Medicine, Denver, CO, USA Environmental Occupational Health Dept, School of Public Health, University of Colorado, Denver, CO, USA
- Resource Type
- Journal article
- Publication Details
- The European respiratory journal, Vol.47(6), pp.1797-1808
- DOI
- 10.1183/13993003.01469-2015
- PMID
- 27103383
- PMCID
- PMC5134922
- ISSN
- 0903-1936
- eISSN
- 1399-3003
- Grant note
- K12 HL090147 / NHLBI NIH HHS P01 ES011810 / NIEHS NIH HHS K01 ES020857 / NIEHS NIH HHS UL1 TR001082 / NCATS NIH HHS R01 ES023826 / NIEHS NIH HHS
- Language
- English
- Date published
- 06/2016
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094379602771
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