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Erschienen in: Intensive Care Medicine 1/2005

01.01.2005 | Experimental

Active transforming growth factor-β1 activates the procollagen I promoter in patients with acute lung injury

verfasst von: G. R. Scott Budinger, Navdeep S. Chandel, Helen K. Donnelly, James Eisenbart, Monica Oberoi, Manu Jain

Erschienen in: Intensive Care Medicine | Ausgabe 1/2005

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Abstract

Objective

Fibroproliferation markers like procollagen I predict mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes.

Design

Prospective controlled study of ALI/ARDS.

Setting

Intensive care units and laboratory of a university hospital.

Patients and participants

Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients.

Interventions

Bronchoalveolar lavage fluid was collected within 48 h of intubation from ALI/ARDS patients. BALF was also collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema. Human lung fibroblasts were transfected with a procollagen I promoter-luciferase construct and incubated with BALF; procollagen I promoter activity was then measured. BALF active TGF-β1 levels were measured by ELISA.

Results

Twenty-nine ARDS patients, nine negative and six positive controls were enrolled. BALF from ARDS patients induced 41% greater procollagen I promoter activation than that from negative controls (p<0.05) and a TGF-β1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-β1 levels in the ARDS group compared to negative controls (−1.056 log10±0.1415 vs −1.505 log10±0.1425) (p<0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-β1 levels were associated with more ventilator-free and ICU-free days.

Conclusions

Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I promoter, which is due partly to TGF-β1. Activated TGF-β1 may impact ARDS outcome independent of its effect on procollagen I activation.
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Metadaten
Titel
Active transforming growth factor-β1 activates the procollagen I promoter in patients with acute lung injury
verfasst von
G. R. Scott Budinger
Navdeep S. Chandel
Helen K. Donnelly
James Eisenbart
Monica Oberoi
Manu Jain
Publikationsdatum
01.01.2005
Verlag
Springer-Verlag
Erschienen in
Intensive Care Medicine / Ausgabe 1/2005
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-004-2503-2

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