Am. J. Respir. Cell Mol. Biol.,
Volume 19, Number 3, September, 1998 498-506
Cadmium Inhibits Proteoglycan and Procollagen Production by Cultured
Human Lung Fibroblasts
Rachel C.
Chambers,
Geoffrey J.
Laurent,
and
Gunilla
Westergren-Thorsson
Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, University College Medical School, Rayne Institute,
London, United Kingdom; and Department of Cell and Molecular Biology, Lund University, Lund, Sweden
Chronic inhalation of cadmium at the workplace or in cigarette smoke is associated with emphysema, a
disease characterized by extensive disruption of lung connective tissue. We have previously shown that
cadmium, at noncytotoxic doses, inhibits fibroblast procollagen production in vitro, with maximal inhibitory effects of 69 ± 6% (P < 0.01) at 30 µM cadmium chloride (CdCl2). In this paper we show that at
similar doses, cadmium also inhibits proteoglycan synthesis, with values reduced by between 36 ± 4%
(P < 0.01) and 42 ± 6% (P < 0.01) for proteoglycans secreted into the culture media and associated with
the cell layer, respectively. The greatest inhibition was obtained for the major matrix-associated proteoglycans, versican, decorin, and the large heparan sulfate proteoglycans, with synthesis values reduced by between 60 and 70%. Biglycan and other heparan sulfate proteoglycans were also affected, with synthesis
values reduced by between 25 and 45%. In contrast, total protein synthesis was unaffected. Furthermore,
effects of cadmium at the protein level were mirrored by reduction in messenger RNA levels for 
1(I) procollagen, versican, and decorin. These data support the hypothesis that cadmium may play an important
role in the pathogenesis of emphysema associated with chronic inhalation of cadmium fumes by inhibiting
the production of connective tissue proteins.
