Neutrophilic inflammation in the lung protects against infectious disease, and usually resolves spontaneously after removal of the inflammatory stimulus. However, much lung disease is caused by a failure of resolution of neutrophilic inflammation. Our laboratory is seeking an understanding of the biochemical basis of inflammation resolution, using the zebrafish model system. Zebrafish larvae are transparent, allowing visualization of GFP (green fluorescent protein)-labelled leucocytes during inflammation in vivo, and they can be readily manipulated by a range of forward and reverse genetic techniques. This combination of advantages makes zebrafish a powerful tool for the study of in vivo inflammatory processes. Using this model, we have visualized the process of inflammation resolution in vivo, and identified a role for apoptosis in this process. In addition, we have performed a forward genetic screen for mutants with defective resolution of inflammation, and reverse genetic experiments examining the influence of candidate genes on inflammation resolution. We have established a platform for screening for compounds with anti-inflammatory activity, which has yielded a number of interesting leads. Looking forward to succeed in the future, we are working at combining mutants, transgenes and pharmacological agents to dissect the biochemical basis of inflammation resolution, and to identify compounds that might be used to treat patients with respiratory disease.
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Conference Article|
July 22 2009
Using in vivo zebrafish models to understand the biochemical basis of neutrophilic respiratory disease
Jane S. Martin;
Jane S. Martin
1MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Western Bank, Sheffield S10 2TN, U.K.
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Stephen A. Renshaw
Stephen A. Renshaw
1
1MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Western Bank, Sheffield S10 2TN, U.K.
1To whom correspondence should be addressed (email s.a.renshaw@sheffield.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 30 2009
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem Soc Trans (2009) 37 (4): 830–837.
Article history
Received:
March 30 2009
Citation
Jane S. Martin, Stephen A. Renshaw; Using in vivo zebrafish models to understand the biochemical basis of neutrophilic respiratory disease. Biochem Soc Trans 1 August 2009; 37 (4): 830–837. doi: https://doi.org/10.1042/BST0370830
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