Person: Norris, Paul
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Norris, Paul
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Publication Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity(Nature Publishing Group UK, 2018) Werz, Oliver; Gerstmeier, Jana; Libreros, Stephania; De la Rosa, Xavier; Werner, Markus; Norris, Paul; Chiang, Nan; Serhan, CharlesProinflammatory eicosanoids (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPM) are temporally regulated during infections. Here we show that human macrophage phenotypes biosynthesize unique lipid mediator signatures when exposed to pathogenic bacteria. E. coli and S. aureus each stimulate predominantly proinflammatory 5-lipoxygenase (LOX) and cyclooxygenase pathways (i.e., leukotriene B4 and prostaglandin E2) in M1 macrophages. These pathogens stimulate M2 macrophages to produce SPMs including resolvin D2 (RvD2), RvD5, and maresin-1. E. coli activates M2 macrophages to translocate 5-LOX and 15-LOX-1 to different subcellular locales in a Ca2+-dependent manner. Neither attenuated nor non-pathogenic E. coli mobilize Ca2+ or activate LOXs, rather these bacteria stimulate prostaglandin production. RvD5 is more potent than leukotriene B4 at enhancing macrophage phagocytosis. These results indicate that M1 and M2 macrophages respond to pathogenic bacteria differently, producing either leukotrienes or resolvins that further distinguish inflammatory or pro-resolving phenotypes.Publication ERV1 Overexpression in Myeloid Cells Protects against High Fat Diet Induced Obesity and Glucose Intolerance(Nature Publishing Group UK, 2017) Sima, Corneliu; Montero, Eduardo; Nguyen, Daniel; Freire, Marcelo; Norris, Paul; Serhan, Charles; Van Dyke, ThomasNon-resolving inflammation is a central pathologic component of obesity, insulin resistance, type 2 diabetes and associated morbidities. The resultant hyperglycemia is deleterious to the normal function of many organs and its control significantly improves survival and quality of life for patients with diabetes. Macrophages play critical roles in both onset and progression of obesity-associated insulin resistance. Here we show that systemic activation of inflammation resolution prevents from morbid obesity and hyperglycemia under dietary overload conditions. In gain-of-function studies using mice overexpressing the human resolvin E1 receptor (ERV1) in myeloid cells, monocyte phenotypic shifts to increased patrolling-to-inflammatory ratio controlled inflammation, reduced body weight gain and protected from hyperglycemia on high-fat diet. Administration of a natural ERV1 agonist, resolvin E1, recapitulated the pro-resolving actions gained by ERV1 overexpression. This protective metabolic impact is in part explained by systemic activation of resolution programs leading to increased synthesis of specialized pro-resolving mediators.Publication Author Correction: ERV1 Overexpression in Myeloid Cells Protects against High Fat Diet Induced Obesity and Glucose Intolerance(Nature Publishing Group UK, 2018) Sima, Corneliu; Montero, Eduardo; Nguyen, Daniel; Freire, Marcelo; Norris, Paul; Serhan, Charles; Van Dyke, Thomas