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The Acute Respiratory Distress Syndrome

A Role for Transforming Growth Factor-ß1

Division of Pulmonary and Critical Care Medicine, Dorothy M. Davis Heart and Lung Research Institute; and Department of Pathology, The Ohio State University, Columbus, Ohio

Address correspondence to: Ruairi J. Fahy, 201 The Davis Heart & Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210-1252. E-mail: fahy-1{at}medctr.osu.edu

This article has an online data supplement, which is accessible from this issue's table of contents online at www.atsjournals.org

The acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality. Enhanced fibrosis and elevated procollagen III levels have been linked to increased mortality. We hypothesized that transforming growth factor (TGF)-ß1 may play an important role in ARDS, given its role in stimulating fibrosis. Using reverse transcriptase in situ polymerase chain reaction (RT in situ PCR) and immunohistochemistry, we analyzed lung tissue from four fibroproliferative ARDS cases and control subjects. We also compared active TGF-ß1 levels in the bronchoalveolar lavage (BAL) fluid of 13 de novo ARDS cases, and 7 normal control subjects. RT in situ PCR showed TGF-ß1 mRNA expression in fibroproliferative ARDS cases. Immunohistochemistry confirmed protein expression in these samples. Controls were negative for both techniques. In the newly enrolled ARDS cases, TGF-ß1 levels, as measured by luciferase assay, were elevated in the 11 of 13 samples, averaging 98 ± 40 pg/mg protein. Controls had no detectable TGF-ß1 activity. These data suggest that activation of TGF-ß1 may be important in the early phases of acute lung injury in addition to driving fibroproliferation. These data may lead to new therapeutic approaches in ARDS through more targeted inhibition of fibrosis.

Abbreviations: acute respiratory distress syndrome, ARDS • bronchoalveolar lavage, BAL • fetal bovine serum, FBS • mink lung epithelial cell, MLEC • matrix metalloproteinase, MMP • reverse transcriptase in situ polymerase chain reaction, RT in situ PCR • transforming growth factor-ß1, TGF-ß1

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