Genomic analysis of human lung fibroblasts exposed to vanadium pentoxide to identify candidate genes for occupational bronchitis.
BACKGROUND
Exposure to vanadium pentoxide (V2O5) is a cause of occupational bronchitis. We evaluated gene expression profiles in cultured human lung fibroblasts exposed to V2O5 in vitro in order to identify candidate genes that could play a role in inflammation, fibrosis, and repair during the pathogenesis of V2O5-induced bronchitis.


METHODS
Normal human lung fibroblasts were exposed to V2O5 in a time course experiment. Gene expression was measured at various time points over a 24 hr period using the Affymetrix Human Genome U133A 2.0 Array. Selected genes that were significantly changed in the microarray experiment were validated by RT-PCR.


RESULTS
V2O5 altered more than 1,400 genes, of which ~300 were induced while >1,100 genes were suppressed. Gene ontology categories (GO) categories unique to induced genes included inflammatory response and immune response, while GO categories unique to suppressed genes included ubiquitin cycle and cell cycle. A dozen genes were validated by RT-PCR, including growth factors (HBEGF, VEGF, CTGF), chemokines (IL8, CXCL9, CXCL10), oxidative stress response genes (SOD2, PIPOX, OXR1), and DNA-binding proteins (GAS1, STAT1).


CONCLUSIONS
Our study identified a variety of genes that could play pivotal roles in inflammation, fibrosis and repair during V2O5-induced bronchitis. The induction of genes that mediate inflammation and immune responses, as well as suppression of genes involved in growth arrest appear to be important to the lung fibrotic reaction to V2O5.
Ingram
Jennifer L
JL
The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA. jennifer.ingram@duke.edu <jennifer.ingram@duke.edu>
Antao-Menezes
Aurita
A
Turpin
Elizabeth A
EA
Wallace
Duncan G
DG
Mangum
James B
JB
Pluta
Linda J
LJ
Thomas
Russell S
RS
Bonner
James C
JC
D001991:Bronchitis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002874:Chromosome Mapping / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009784:Occupational Diseases / Q000235:genetics / Q000378:metabolism*; D016273:Occupational Exposure / Q000009:adverse effects; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D017968:Vanadium Compounds / Q000506:poisoning*
D020543:Proteome; D017968:Vanadium Compounds; C066075:vanadium pentoxide