Real time changes in the expression of eicosanoid synthesizing enzymes during inflammation

Abstract

Immune responses during inflammation involve complex, well-coordinated lipid signaling pathways. Eicosanoids are a class of lipid signaling molecules derived from polyunsaturated fatty acids such as arachidonic acid and constitute a major network that controls inflammation and its subsequent resolution. Arachidonic acid is metabolized by enzymes in three different pathways to form a variety of lipid metabolites that can be either pro- or anti-inflammatory. Therefore, an understanding of the time-dependent gene expression, lipid metabolite profiles and cytokine profiles during the initial inflammatory response is necessary, as it will allow for the design of time-dependent therapeutics. Herein, we investigate the multi-level regulation of this process. After stimulating RAW 264.7 cells, a mouse-derived macrophage cell line commonly used to examine inflammatory responses, we examine the gene expression of 44 relevant lipid metabolizing enzymes from the different eicosanoid synthesizing classes. We also measure the formation of lipid metabolites and production of cytokines at selected time points. Results reveal a dynamic relationship between the time-course of inflammation dependent gene expression of the three eicosanoid synthesizing enzymes.