Active transforming growth factor-beta1 activates the procollagen I promoter in patients with acute lung injury.

Abstract

ObjectiveFibroproliferation 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.DesignProspective controlled study of ALI/ARDS.SettingIntensive care units and laboratory of a university hospital.Patients and participantsAcute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients.InterventionsBronchoalveolar 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.ResultsTwenty-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.ConclusionsBronchoalveolar 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.Electronic Supplementary MaterialSupplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-004-2503-2