Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis.
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.
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.org.
Li
L
Li
Dept of Medicine, National Jewish Health, Denver, CO, USA.
Lori J
LJ
Silveira
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.
Nabeel
N
Hamzeh
Dept of Medicine, National Jewish Health, Denver, CO, USA.
May
M
Gillespie
Dept of Medicine, National Jewish Health, Denver, CO, USA.
Peggy M
PM
Mroz
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.
Annyce S
AS
Mayer
Dept of Medicine, National Jewish Health, Denver, CO, USA.
Tasha E
TE
Fingerlin
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.
Lisa A
LA
Maier
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001607:Berylliosis / Q000235:genetics / Q000503:physiopathology*; D001608:Beryllium / Q000009:adverse effects*; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008171:Lung Diseases / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012507:Sarcoidosis / Q000235:genetics / Q000503:physiopathology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D001608:Beryllium