Active transforming growth factor-beta 1 activates the procollagen I promoter in patients with acute lung injury

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-beta1 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-beta 1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-beta 1 levels in the ARDS group compared to negative controls ( - 1.056 log(10)+/- 0.1415 vs - 1.505 log(10)+/-0.1425) ( p< 0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-beta1 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-beta1. Activated TGF-beta1 may impact ARDS outcome independent of its effect on procollagen I activation.