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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)121-128
Number of pages8
JournalIntensive Care Medicine
Volume31
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • Acute respiratory distress syndrome
  • Bronchoalveolar lavage
  • Fibroproliferation
  • Procollagen I
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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