Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture

• Published in: American journal of physiology. Lung cellular and molecular physiology 2001-10, Vol.281 (4), p.868-L878
• Main Authors: Zhu, Y. K, Liu, X. D, Skold, C. M, Umino, T, Wang, H. J, Spurzem, J. R, Kohyama, T, Ertl, R. F, Rennard, S. I
• Format: Article
• Language: English
• Subjects: Animals; Cell Count; Cell Culture Techniques - methods; Cells, Cultured; Collagen - metabolism; Cytokines - metabolism; Cytokines - pharmacology; Drug Synergism; Emphysema - metabolism; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - enzymology; Gels; Humans; Interferon-gamma - metabolism; Interferon-gamma - pharmacology; Interleukin-1 - metabolism; Interleukin-1 - pharmacology; Leukocyte Elastase - metabolism; Leukocyte Elastase - pharmacology; Lung - cytology; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 3 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medicin och hälsovetenskap; Rats; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tissue Inhibitor of Metalloproteinase-2 - metabolism; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2001.281.4.l868

1  Jincheng Hospital, Lanzhou 730050, China; 2  University of Nebraska Medical Center, Omaha, Nebraska 68198-5125; and 3  Karolinska Institute, S-171 76 Stockholm, Sweden Proteolytic degradation of extracellular matrix is thought to play an important role in many lung disorders. In the current study, human lung fibroblasts were cast into type I collagen gels and floated in medium containing elastase, cytomix (combination of tumor necrosis factor- , interleukin-1 , and interferon- ), or both. After 5 days, gel collagen content was determined by measuring hydroxyproline. Elastase alone did not result in collagen degradation, but in the presence of fibroblasts, elastase reduced hydroxyproline content to 75.2% ( P