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Inflammatory Findings

Why bioactive lipids sometimes ‘signal’ inflammatory responses.

Scientific interest in bioactive lipids, the critically important oils and fats found in all living tissue, has grown rapidly in recent years, thanks in large part to advances in liquid-chromatography tandem mass spectrometry, or LC-MSMS.

In the hands of experts, LC-MSMS techniques are opening new vistas in sampling and analyzing bioactive lipids — molecules that use “signaling” properties to guide vital bodily functions such as cell division, brain development, fertilization and various vascular and immune processes.

Charles Brown, an associate professor of veterinary pathobiology at MU, is among those who see vast potential in lipid studies, particularly in the area of his research specialty, inflammation. “Many diseases, such as arthritis, cardiovascular disease and diabetes are associated with chronic inflammation,” says Brown. “The first step in finding an effective treatment is to understand the basics of an inflammatory response, including the role of bioactive lipids.”

In a recent study, Brown and his collaborators examined mice infected with Borrelia burgdorferi, the bacteria responsible for Lyme disease and its associated arthritis. Eicosanoids, bioactive lipids known to play a role in inflammatory disease, were extracted from mice that displayed symptoms of Lyme arthritis, as well as from those that showed no symptoms. The researchers, using an advanced form of LC-MSMS analysis, then tracked the production of over 100 different eicosanoids in the joints of infected mice. They found heightened amounts of specific eicosanoids in the samples of mice with Lyme arthritis and, more importantly, were able to correlate these levels with the severity of inflammation in mice that were arthritis-afflicted.

The findings, published in the June edition of the Journal of Biological Chemistry, could lay the groundwork for improving medications that block lipid-signaled pain and swelling.

“The process of inflammation is not a passive event, but instead is a coordinated, orderly process actively signaled by specific protein and lipid molecules,” Brown says. “Previous studies investigating eicosanoids have focused on singular pathways or phases of the inflammatory response. These studies provided an incomplete picture and gave the impression that some bioactive lipids function in isolation. In our study, we were able to measure virtually all of the known eicosanoids at the same time and examine a more complete picture of the inflammatory response.”

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