Lipopolysaccharide increases fibronectin production and release from cultured lung fibroblasts partially through proteolytic activity

• Published in: The Journal of laboratory and clinical medicine 1996-05, Vol.127 (5), p.448-455
• Main Authors: Adachi, Y., Mio, T., Striz, I., Carnevali, S., Romberger, D.J., Spurzem, J.R., Heires, P., Illig, M.G., Ertl, R.F., Rennard, S.I.
• Format: Article
• Language: English
• Subjects: Bacterial diseases; Biological and medical sciences; Cell Line; Cycloheximide - pharmacology; Embryo, Mammalian; Endopeptidases - metabolism; Escherichia coli; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibronectins - biosynthesis; Fibronectins - secretion; General aspects; Humans; Infectious diseases; Kinetics; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; Lung - drug effects; Lung - metabolism; Medical sciences; Protein Synthesis Inhibitors - pharmacology
• ISSN: 0022-2143; 1532-6543
• DOI: 10.1016/S0022-2143(96)90062-1

Fibronectin is a major product of fibroblasts and can mediate diverse functions including wound healing. Chronic bacterial infections are generally associated with a marked decrease in the ability to repair. We therefore hypothesized that bacterial endotoxin, lipopolysaccharide (LPS), might alter fibroblast fibronectin production. LPS augmented fibronectin production by fibroblasts and also stimulated the release of fibronectin from cell layers. An increase in new protein synthesis appeared to account for part of the increased fibronectin, because the inhibitor of protein synthesis, cycloheximide, inhibited the increase in total production of fibronectin. Cycloheximide did not attenuate the increased release of fibronectin into the culture medium. This increased release appeared to be caused, at least in part, by fragmentation of fibronectin by proteases contained in LPS preparations. In this regard all preparations of LPS tested were found to cleave fibronectin. Finally, zymograms indicated that LPS could also cleave gelatin with at least two bands of proteolytic activity but that it did not cleave bovine serum albumin or ovalbumin. These results indicate that the ability of bacterial products to alter fibronectin production and to degrade this macromolecule may account for altered wound repair that occurs with chronic bacterial infection.