A new study of cellular biology in mice unexpectedly turned up a potential pathway to help patients with rheumatoid arthritis (RA).
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The study, “Peroxisomal Lipid Synthesis Regulates Inflammation by Sustaining Neutrophil Membrane Phospholipid Composition and Viability,” published in January’s Cell Metabolism, found that by controlling neutrophils—a well-known marker of inflammation—researchers may be able to use a previously unrecognized pathway to improve immunometabolism.1
“This is a proof-of-principle experiment that stumbled on a completely unexpected way to control the production of neutrophils,” says Clay Semenkovich, MD, chief of the Division of Endocrinology, Metabolism and Lipid Research at Washington University in St. Louis. “You wouldn’t want someone’s neutrophils to go completely away, but you could do small-molecule screening for inhibition of the particular pathways targeted in our work and then titrate the amount that you give.
“In somebody who had very robust RA, you might be able to decrease the concentration of neutrophils in a joint. Or you could take a small molecule inhibitor and inject it into a damaged joint to decrease the ability of neutrophils to damage the synovial surface.”
Dr. Semenkovich says researchers examined the bone marrow of dead mice and “serendipitously” found that when cells make fatty acids, they channel them to peroxisomes where, when they’re modified in a certain way, ether lipids are created. Interfering with that pathway could one day provide insights on screening and treatment for RA patients.
“Ether lipid signatures could be predictive of people who would have inflammatory processes. Lowering ether lipids could represent a potential strategy to decrease the inflammatory processes for people who already have the disease,” Dr. Semenkovich adds. “It is one more example of doing basic research and coming up with unexpected observations that have the potential to decrease suffering in people who have arthritis.”
Richard Quinn is a freelance writer in New Jersey.
1. Lodhi IJ, Wei X, Yin L, et al. Peroxisomal lipid synthesis regulates inflammation by sustaining neutrophil membrane phospholipid composition and viability. Cell Metabolism. 2015 Jan;21(1):51–64.