Impairment of alveolar macrophage transcription in idiopathic pulmonary fibrosis.
BACKGROUND
Alveolar macrophages are inflammatory cells that may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is characterized by excessive alveolar aggregation of cells and extracellular matrix proteins.


OBJECTIVE
To identify potential molecular mechanisms of IPF.


METHODS
To examine large-scale gene expression, messenger RNA isolated from alveolar macrophages and peripheral blood mononuclear cells from subjects with IPF and normal volunteers was hybridized to cDNA filters.


RESULTS
We showed that in IPF there is global down-regulation of gene expression in alveolar macrophages but not in blood monocytes. Nuclear run-on and pulse-chase studies showed that alveolar macrophages had significantly reduced transcription (p < 0.01). No significant difference in RNA degradation was found between subjects with IPF and normal volunteers. Western blot analyses revealed that concentrations of transcription factor II-H, a general transcription factor, were significantly lower in alveolar macrophages from subjects with IPF than in those from normal volunteers (p = 0.012).


CONCLUSIONS
Impaired transcription in IPF is associated with decreased concentrations of transcription factor II-H in alveolar macrophages and may alter the intraalveolar milieu in IPF.
Ren
Ping
P
Pulmonary--Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rosas
Ivan O
IO
Macdonald
Sandra D
SD
Wu
Hai-Ping
HP
Billings
Eric M
EM
Gochuico
Bernadette R
BR
D015415:Biomarkers; D015152:Blotting, Northern; D015153:Blotting, Western; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D016676:Macrophages, Alveolar / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D051758:Transcription Factor TFIIH / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D015415:Biomarkers; D012333:RNA, Messenger; D051758:Transcription Factor TFIIH