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Impairment of alveolar macrophage transcription in idiopathic pulmonary fibrosis.


ABSTRACT: 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.To identify potential molecular mechanisms of IPF.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.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).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.

SUBMITTER: Ren P 

PROVIDER: S-EPMC1899274 | biostudies-other | 2007 Jun

REPOSITORIES: biostudies-other

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Impairment of alveolar macrophage transcription in idiopathic pulmonary fibrosis.

Ren Ping P   Rosas Ivan O IO   Macdonald Sandra D SD   Wu Hai-Ping HP   Billings Eric M EM   Gochuico Bernadette R BR  

American journal of respiratory and critical care medicine 20070301 11


<h4>Rationale</h4>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.<h4>Objectives</h4>To identify potential molecular mechanisms of IPF.<h4>Methods</h4>To examine large-scale gene expression, messenger RNA isolated from alveolar macrophages and peripheral blood mononuclear cells from subjects with IPF and normal volunteers  ...[more]

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