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Inflammation Dampened by Gelatinase A Cleavage of Monocyte Chemoattractant Protein-3
Abstract
Tissue degradation by the matrix metalloproteinase gelatinase A is pivotal to inflammation and metastases. Recognizing the catalytic importance of substrate-binding exosites outside the catalytic domain, we screened for extracellular substrates using the gelatinase A hemopexin domain as bait in the yeast two-hybrid system. Monocyte chemoattractant protein–3 (MCP-3) was identified as a physiological substrate of gelatinase A. Cleaved MCP-3 binds to CC-chemokine receptors–1, –2, and –3, but no longer induces calcium fluxes or promotes chemotaxis, and instead acts as a general chemokine antagonist that dampens inflammation. This suggests that matrix metalloproteinases are both effectors and regulators of the inflammatory response.
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Citations
Cited by
New functions for the matrix metalloproteinases in cancer progression
Egeblad, M., & Werb, Z. (2002) · Nature Reviews Cancer · doi:10.1038/nrc745 · Cited by 6,108
Visse, R., & Nagase, H. (2003) · Circulation Research · doi:10.1161/01.res.0000070112.80711.3d · Cited by 4,575
How Matrix Metalloproteinases Regulate Cell Behavior
Sternlicht, M. D., & Werb, Z. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.463 · Cited by 3,959
Matrix metalloproteinases and the regulation of tissue remodelling
Page-McCaw, A., Ewald, A. J., & Werb, Z. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2125 · Cited by 2,630
Inflammation in Wound Repair: Molecular and Cellular Mechanisms
Eming, S. A., Krieg, T., & Davidson, J. M. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700701 · Cited by 2,429
Metadata
- Authors
- McQuibban, G. A., Gong, J.-H., Tam, E. M., McCulloch, C. A. G., Clark-Lewis, I., & Overall, C. M.
- Venue
- Science
- Published
- 2000-08-18
- Volume
- 289
- Issue
- 5482
- Pages
- 1202-1206
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2155093913
- Cited by
- 772
- References
- 0
- FWCI
- 15.41
- Type
- journal article
- Language
- en
- Open access
- closed
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- McQuibban, G. A., Gong, J.-H., Tam, E. M., McCulloch, C. A. G., Clark-Lewis, I., & Overall, C. M. (2000). Inflammation Dampened by Gelatinase A Cleavage of Monocyte Chemoattractant Protein-3. Science. https://doi.org/10.1126/science.289.5482.1202
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
