5 results on '"Norris, Paul"'
Search Results
2. Phospholipase A2 regulates eicosanoid class switching during inflammasome activation
- Author
-
Norris, Paul C, Gosselin, David, Reichart, Donna, Glass, Christopher K, and Dennis, Edward A
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Animals ,Aspirin ,Celecoxib ,Cell Line ,Transformed ,Cyclooxygenase 2 Inhibitors ,Cyclooxygenase Inhibitors ,Eicosanoids ,Group IV Phospholipases A2 ,Hydroxyeicosatetraenoic Acids ,Inflammasomes ,Interleukin-1 ,Lipidoses ,Macrophages ,Male ,Mice ,Mice ,Inbred C57BL ,Pyrazoles ,Receptors ,Purinergic P2X7 ,Signal Transduction ,Sulfonamides ,Toll-Like Receptor 4 ,lipidomics ,enzyme coupling ,membrane remodeling - Abstract
Initiation and resolution of inflammation are considered to be tightly connected processes. Lipoxins (LX) are proresolution lipid mediators that inhibit phlogistic neutrophil recruitment and promote wound-healing macrophage recruitment in humans via potent and specific signaling through the LXA4 receptor (ALX). One model of lipoxin biosynthesis involves sequential metabolism of arachidonic acid by two cell types expressing a combined transcellular metabolon. It is currently unclear how lipoxins are efficiently formed from precursors or if they are directly generated after receptor-mediated inflammatory commitment. Here, we provide evidence for a pathway by which lipoxins are generated in macrophages as a consequence of sequential activation of toll-like receptor 4 (TLR4), a receptor for endotoxin, and P2X7, a purinergic receptor for extracellular ATP. Initial activation of TLR4 results in accumulation of the cyclooxygenase-2-derived lipoxin precursor 15-hydroxyeicosatetraenoic acid (15-HETE) in esterified form within membrane phospholipids, which can be enhanced by aspirin (ASA) treatment. Subsequent activation of P2X7 results in efficient hydrolysis of 15-HETE from membrane phospholipids by group IVA cytosolic phospholipase A2, and its conversion to bioactive lipoxins by 5-lipoxygenase. Our results demonstrate how a single immune cell can store a proresolving lipid precursor and then release it for bioactive maturation and secretion, conceptually similar to the production and inflammasome-dependent maturation of the proinflammatory IL-1 family cytokines. These findings provide evidence for receptor-specific and combinatorial control of pro- and anti-inflammatory eicosanoid biosynthesis, and potential avenues to modulate inflammatory indices without inhibiting downstream eicosanoid pathways.
- Published
- 2014
3. Specific oxylipins enhance vertebrate hematopoiesis via the receptor GPR132
- Author
-
Lahvic, Jamie L., Ammerman, Michelle, Li, Pulin, Blair, Megan C., Stillman, Emma R., Fast, Eva M., Robertson, Anne L., Christodoulou, Constantina, Perlin, Julie R., Yang, Song, Chiang, Nan, Norris, Paul C., Daily, Madeleine L., Redfield, Shelby E., Chan, Iris T., Chatrizeh, Mona, Chase, Michael E., Weis, Olivia, Zhou, Yi, Serhan, Charles N., and Zon, Leonard I.
- Published
- 2018
4. Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling
- Author
-
Norris, Paul C and Dennis, Edward A
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Industrial Biotechnology ,Complementary and Integrative Health ,Nutrition ,Dietary Supplements ,Prevention ,2.1 Biological and endogenous factors ,Adenosine Triphosphate ,Animals ,Arachidonic Acid ,Blotting ,Western ,Cell Line ,Cell Membrane ,Cells ,Cultured ,Docosahexaenoic Acids ,Eicosanoids ,Fatty Acids ,Omega-3 ,Fatty Acids ,Unsaturated ,Gas Chromatography-Mass Spectrometry ,Lipopolysaccharides ,Lipoxygenase ,Macrophages ,Macrophages ,Peritoneal ,Male ,Membrane Lipids ,Mice ,Phospholipases A2 ,Prostaglandin-Endoperoxide Synthases ,Receptors ,Purinergic P2X7 ,Signal Transduction ,Toll-Like Receptor 4 - Abstract
Dietary fish oil containing ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), elicit cardioprotective and anti-inflammatory effects through unresolved mechanisms that may involve competition and inhibition at multiple levels. Here, we report the effects of arachidonic acid (AA), EPA, and DHA supplementation on membrane incorporation, phospholipase A(2) catalyzed release, and eicosanoid production in RAW264.7 macrophages. Using a targeted lipidomics approach, we observed that Toll-like receptor 4 and purinergic receptor activation of supplemented cells leads to the release of 22-carbon fatty acids that potently inhibit cyclooxygenase pathways. This inhibition was able to shunt metabolism of AA to lipoxygenase pathways, augmenting leukotriene and other lipoxygenase mediator synthesis. In resident peritoneal macrophages, docosapentaenoic acid (DPA) was responsible for cyclooxygenase inhibition after EPA supplementation, offering fresh insights into how EPA exerts anti-inflammatory effects indirectly through elongation to 22-carbon DPA.
- Published
- 2012
5. Phospholipase A2 regulates eicosanoid class switching during inflammasome activation.
- Author
-
Norris, Paul C., Gosselin, David, Reichart, Donna, Glass, Christopher K., and Dennis, Edward A.
- Subjects
- *
PHOSPHOLIPASE A2 , *LIPOXINS , *BIOSYNTHESIS , *HYDROXYEICOSATETRAENOIC acid , *EICOSANOIDS - Abstract
Initiation and resolution of inflammation are considered to be tightly connected processes. Lipoxins (LX) are proresolution lipid mediators that inhibit phlogistic neutrophil recruitment and promote wound-healing macrophage recruitment in humans via potent and specific signaling through the LXA4 receptor (ALX). One model of lipoxin biosynthesis involves sequential metabolism of arachidonic acid by two cell types expressing a combined transcellular metabolon. It is currently unclear how lipoxins are efficiently formed from precursors or if they are directly generated after receptor-mediated inflammatory commitment. Here, we provide evidence for a pathway by which lipoxins are generated in macrophages as a consequence of sequential activation of toll-like receptor 4 (TLR4), a receptor for endotoxin, and P2X7, a purinergic receptor for extracellular ATP. Initial activation of TLR4 results in accumulation of the cyclooxygenase-2-derived lipoxin precursor 15-hydroxyeicosatetraenoic acid (15-HETE) in esterified form within membrane phospholipids, which can be enhanced by aspirin (ASA) treatment. Subsequent activation of P2X7 results in efficient hydrolysis of 15-HETE from membrane phospholipids by group IVA cytosolic phospholipase A2, and its conversion to bio-active lipoxins by 5-lipoxygenase. Our results demonstrate how a single immune cell can store a proresolving lipid precursor and then release it for bioactive maturation and secretion, conceptually similar to the production and inflammasome-dependent maturation of the proinflammatory IL-1 family cytokines. These findings provide evidence for receptor-specific and combinatorial control of pro- and anti-inflammatory eicosanoid biosynthesis, and potential avenues to modulate inflammatory indices without inhibiting downstream eicosanoid pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
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