What is it about?
Polyunsaturated fatty acids are precursors for the large family of bioactive lipid mediators. Some of these lipid mediators (i.e. prostaglandins, leukotrienes) promote inflammatory processes and contribute to inflammation-related diseases such as arthritis, asthma and cardiovascular diseases, while other, newly discovered, lipid mediators (termed specialized pro-resolving mediators = SPM) have opposing effects and actively terminate inflammation and support tissue repair. All these lipid mediators are formed by enzymes termed lipoxygenases and cyclooxygenases within a complex biosynthetic network with marked cross-talk. These enzymes are targeted by anti-inflammatory drugs such as ibuprofen or celecoxib that are used in the clinics to treat inflammatory disorders, fever and pain, apparently due to suppression of the formation of pro-inflammatory lipid mediators. But how interference of these anti-inflammatory drugs with cyclooxygenases and lipoxygenases influences the formation of inflammation-resolving SPM and how they affect the overall lipid mediator network is unknown, partly because suitable biological test systems and analytical tools were not available yet. Here, we present a convenient experimental approach using bacteria-stimulated immune cells (i.e. macrophages) that occur either as pro-inflammatory subtype (M1) producing mainly prostaglandins and leukotrienes or as anti-inflammatory subtype (M2) generating primarily SPM. Our results led to important, partly unexpected insights into how these anti-inflammatory drugs modulate the formation of SPM in M2 macrophages. Thus, we document the pharmacological profile of anti-inflammatory drugs and disclose for the first time their ability to manipulate inflammation-resolving molecules, insights that may allow better appraisal of the therapeutic potential of these drugs to intervene with inflammatory disorders.
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This page is a summary of: Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome, The FASEB Journal, May 2019, Federation of American Societies For Experimental Biology (FASEB),
DOI: 10.1096/fj.201802509r.
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