The acute respiratory distress syndrome: a role for transforming growth factor-beta 1.
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)-beta 1 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-beta 1 levels in the bronchoalveolar lavage (BAL) fluid of 13 de novo ARDS cases, and 7 normal control subjects. RT in situ PCR showed TGF-beta 1 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-beta 1 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-beta 1 activity. These data suggest that activation of TGF-beta 1 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.
Fahy
Ruairi J
RJ
Division of Pulmonary and Critical Care Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210-1252, USA. fahy-1@medctr.osu.edu
Lichtenberger
Frank
F
McKeegan
Christine B
CB
Nuovo
Gerard J
GJ
Marsh
Clay B
CB
Wewers
Mark D
MD
D000208:Acute Disease; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000473:pathology* / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D008156:Luciferases