Lab Invest. 2004 May 3 [Epub ahead of print] Related
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Asbestos-derived reactive oxygen species activate TGF-
beta(1).
Pociask DA, Sime PJ, Brody AR.
1Lung Biology Program, Department of Pathology, Tulane
University Health Science Center, New Orleans, LA, USA.
Transforming growth factor-beta(1) (TGF-beta(1)) is a potent
peptide that inhibits epithelial and mesenchymal cell
proliferation and stimulates the synthesis of extracellular
matrix components. This cytokine is produced in a
biologically latent complex bound to a latent-associated
peptide (LAP), and it is the disassociation of this complex
that regulates TGF-beta activity. A number of mechanisms
have been shown to activate TGF-beta(1). We show here that
reactive oxygen species (ROS), generated by the iron in
chrysotile or crocidolite asbestos, mediate the biological
activity of TGF-beta(1). Recombinant human latent TGF-
beta(1) was activated in a cell free system in the presence
of asbestos and ascorbic acid. Latent TGF-beta(1) was
overexpressed in both A549 and mink lung epithelial cell
lines through an adenovirus vector containing the full-
length construct for porcine TGF-beta(1). This latent TGF-
beta(1) was activated in a concentration-dependant fashion
by introducing asbestos into the cell cultures. This
activation was reduced significantly through the use of
superoxide dismutase, catalase or deferoxamine. Amino-acid
constituents of the LAP were oxidized as demonstrated by the
appearance of carbonyls detected by Western analysis. The
oxidized LAP could no longer form a complex with TGF-
beta(1). Our data support the postulate that ROS derived
from asbestos provide a mechanism for activating TGF-beta(1)
in the alveolar environment by oxidizing amino acids in
LAP.Laboratory Investigation advance online publication, 3
May 2004; doi:10.1038/labinvest.3700109
PMID: 15122306 [PubMed - as supplied by publisher]
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