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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2014 February 14; 289(7): 4489.
PMCID: PMC3924309

Establishing a Link between Inflammation and Lipid Metabolism♦

Low Molecular Weight Hyaluronan Activates Cytosolic Phospholipase A2α and Eicosanoid Production in Monocytes and Macrophages

♦ See referenced article, J. Biol. Chem. 2014, 289, 4470–4488

Hyaluronan (HA) is an essential glycosaminoglycan in the extracellular matrix that gets broken down during inflammation. Breakdown of HA leads to the eventual production of eicosanoids, which are lipid mediators also associated with chronic and acute inflammation. In this Paper of the Week, a team led by James H. Shelhamer at the National Institutes of Health worked out the molecular details of how HA fragments lead to production of lipid mediators. They demonstrated that in human monocytes and macrophages, low molecular weight HA stimulated release of arachidonic acid, a key precursor to several classes of lipids. The investigators also showed that low molecular weight HA promoted the phosphorylation of a number of enzymes, including cytosolic phospholipase A2 group IVA (cPLA2α), which liberates arachidonic acid from cell membranes, leading to the production of eicosanoids. Fragmented HA also polarized macrophages toward a proinflammatory M1 phenotype with a unique eicosanoid profile. The authors conclude, “These findings reveal a novel link between HA-mediated inflammation and lipid metabolism.”

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A, proposed model of HA-induced cPLA2α activation and eicosanoid production in monocytes and macrophages. B, impact on macrophage polarization and acquiring an eicosanoid-specific profile.

Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology