After supplementing the mouse macrophages with fatty acids, the scientists stimulated them to produce an inflammatory response. They discovered that omega-3 fatty acids inhibit an enzyme called cyclooxygenase (COX), which produces the prostaglandin hormones that spark inflammation. The action is similar to what happens when one takes an aspirin, which disrupts the COX-2 signaling pathway, thus reducing inflammation and pain.
On the other hand, Dennis and co-author Paul C. Norris, a graduate student in the chemistry and biochemistry department and the molecular pharmacology training program, discovered that omega-3 oils do not inhibit another group of enzymes called lipoxygenases (LOX), which are also produced by stimulated macrophages. One type of generated LOX enzyme in turn produces fat-signaling molecules called leukotrienes, which are pro-inflammatory. But Norris noted that LOX enzymes may also generate anti-inflammatory compounds called resolvins from EPA and DHA.
These observations, he said, are also helpful in identifying potential adverse effects from taking fish oil. Since omega-3 fatty acids possess overlapping functions with COX inhibitor drugs, with well-known side effects, using both in combination can produce unexpected consequences.
It is this parsing of what's happening inside cells that Dennis called "ground-breaking."
"We've been able to look inside a cell, see what fish oils do and determine that the process of inflammation at this level may be manipulatable," he said. "Now, we need to learn if we can fine-tune that process so we can use omega-3 oils to reduce the production of pro-inflammatory prostaglandins and boost the production of anti-inflammatory resolvins."
|Contact: Scott LaFee|
University of California - San Diego