Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture
| Autor: | Yunkui Zhu, Tadashi Kohyama, Hangjun Wang, Takeshi Umino, X. D. Liu, Ronald F. Ertl, S. I. Rennard, John R. Spurzem, C. M. Skold |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Pulmonary and Respiratory Medicine
Physiology Proteolysis medicine.medical_treatment Cell Culture Techniques Cell Count Biology Matrix metalloproteinase Extracellular matrix Interferon-gamma Physiology (medical) medicine Animals Humans Fibroblast Lung Cells Cultured Emphysema Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinase-1 medicine.diagnostic_test Tumor Necrosis Factor-alpha Drug Synergism Cell Biology Fibroblasts Cell biology Rats Cytokine medicine.anatomical_structure Biochemistry Matrix Metalloproteinase 9 Cell culture Neutrophil elastase biology.protein Cytokines Matrix Metalloproteinase 3 Collagen Matrix Metalloproteinase 1 Leukocyte Elastase Gels Type I collagen Interleukin-1 |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 281(4) |
| ISSN: | 1040-0605 |
| Popis: | 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-α, interleukin-1β, and interferon-γ), 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 < 0.01), whereas cytomix alone resulted in reduction of hydroxyproline content to 93% ( P < 0.05). The combination of elastase and cytomix reduced hydroxyproline content to 5.2% ( P < 0.01). α1-Proteinase inhibitor blocked this synergy. Gelatin zymography and Western blot revealed that matrix metalloproteinase (MMP)-1, -3, and -9 were induced by cytomix and activated in the presence of elastase. Tissue inhibitor of metalloproteinase (TIMP)-1 and -2 were also induced by cytomix but were cleaved by elastase. We conclude that a synergistic interaction between cytomix and elastase, mediated through cytokine induction of MMP production and elastase-induced activation of latent MMPs and degradation of TIMPs, can result in a dramatic augmentation of collagen degradation. These findings support the notion that interaction among inflammatory mediators secreted by mononuclear cells and neutrophils can induce tissue cells to degrade extracellular matrix. Such a mechanism may contribute to the protease-anti-protease imbalance in emphysema. |
| Databáze: | OpenAIRE |
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