Lipid Mediators in Health and disease: inflammatory Resolution
cyclo-oxygenase
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Cyclo-oxygenase (COX)-1 and COX-2 enzymes produce a variety of fatty acid mediators called prostanoids. COX enzymes are the targets for non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen and aspirin, some of the most commonly taken drugs in the world.
We originally characterised COX-2 induction in blood vessels. Our research was some of the earliest to indicate that COX-2 may be protective in cardiovascular cells; now a clinically recognised side-effect. We have now gone on to look at the roles of similar lipid metabolising enzymes in vascular and inflammatory cells |
CYP450 / Epoxygnease
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Epoxygenases are CYP450 enzymes that can take a variety of fatty acids as substrates to produce a wide variety of structurally related lipid mediators.
We have shown monocytes and macrophages contain epoxygenases and that these regulate basal inflammation and the phagocytosis of lipid and bacteria (Listeria and E. coli). Part of this protective response is via the epoxygnease activation of the PPAR nuclear receptors, in particular PPARa to give the anti-inflammatory response. |
We now have several ongoing projects on epoxygenase biology. We are examining:
1) The roles of epoxygenase in the regulation of inflammatory resolution:
2) Epoxygenase and its bioactive lipids and their targets in cardiovascular biology
3) Epoxygenase response to experimental uraemia
4) New techniques (high performance capillary electrophoresis) to identify bioactive lipids in biology.
5) Molecular modelling of lipid metabolising enzymes to understand how they produce the mediators they do.
1) The roles of epoxygenase in the regulation of inflammatory resolution:
2) Epoxygenase and its bioactive lipids and their targets in cardiovascular biology
3) Epoxygenase response to experimental uraemia
4) New techniques (high performance capillary electrophoresis) to identify bioactive lipids in biology.
5) Molecular modelling of lipid metabolising enzymes to understand how they produce the mediators they do.
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