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Am J Respir Crit Care Med. 2007 Jun 1;175(11):1151-7. Epub 2007 Mar 1.

Impairment of alveolar macrophage transcription in idiopathic pulmonary fibrosis.

Author information

1
Pulmonary--Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

RATIONALE:

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.

OBJECTIVES:

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.

MEASUREMENTS AND MAIN 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.

PMID:
17332483
PMCID:
PMC1899274
DOI:
10.1164/rccm.200607-958OC
[Indexed for MEDLINE]
Free PMC Article

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