Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation of the airways and extensive oxidative damage. Activated macrophages and neutrophils are elevated in the airways of COPD patients where they sustain the inflammatory response and contribute to tissue damage. During inflammatory reactions arachidonic acid (AA) is released from cell membranes and is converted into the pro-inflammatory prostaglandins and leukotrienes by the action of cycloxygenase-2 (COX-2) and lypoxigenases (LO). It has been recently discovered that COX-2 and LO are able to convert alternative substrates, such as the omega-3 docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA), into mediators that actively repress the inflammatory reactions and promote the resolution of inflammation. Herein we report the formation of new omega-3 electrophilic fatty acid oxo-derivatives by the action of COX-2 and LO in activated human macrophages and stimulated neutrophils. These compounds displayed cytoprotective and anti-inflammatory actions measured as repression of pro-inflammatory enzymes and cytokines and activation of the Nrf2-dependent anti-oxidant response. Data presented herein strongly suggest that electrophilic derivatives of omega-3 fatty acids are generated in inflamed airways of COPD patients where they may contribute to limit tissue damage and inflammatory processes.
- © 2011 ERS