A5029525374- Fatty Acid Research and Health
- Eicosanoids and Hypertension Pharmacology
- Immune Response and Inflammation
- Inflammatory mediators and NSAID effects
- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Asthma and respiratory diseases
- Advanced Glycation End Products research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- S100 Proteins and Annexins
- interferon and immune responses
- Metabolomics and Mass Spectrometry Studies
- Cancer, Lipids, and Metabolism
- Immune cells in cancer
- Cell Adhesion Molecules Research
- Adipokines, Inflammation, and Metabolic Diseases
- Ocular Surface and Contact Lens
- Lipid metabolism and biosynthesis
- Neonatal Respiratory Health Research
- Cytokine Signaling Pathways and Interactions
- Phagocytosis and Immune Regulation
- Macrophage Migration Inhibitory Factor
- Neuropeptides and Animal Physiology
- Sphingolipid Metabolism and Signaling
- Mast cells and histamine
Brigham and Women's Hospital
2016-2025
Harvard University
2016-2025
Harvard University Press
2002-2025
Rockefeller University
2020-2024
Mass General Brigham
2022-2024
Boston University
2000-2023
Yale University
2005-2020
National Institutes of Health
2005-2020
Federation of American Societies for Experimental Biology
1997-2020
Cornell University
1982-2020
Aspirin (ASA) is unique among current therapies because it acetylates cyclooxygenase (COX)-2 enabling the biosynthesis of R-containing precursors endogenous antiinflammatory mediators. Here, we report that lipidomic analysis exudates obtained in resolution phase from mice treated with ASA and docosahexaenoic acid (DHA) (C22:6) produce a novel family bioactive 17R-hydroxy-containing di- tri-hydroxy-docosanoids termed resolvins. Murine brain aspirin produced 17R-hydroxydocosahexaenoic as did...
Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with ω-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array lipid signals. Human endothelial cells upregulated COX-2 ASA converted C20:5 18R-hydroxyeicosapentaenoic...
Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved detection bacteria and viruses, relatively little is known about their function response to eukaryotic microorganisms. Here we identify a profilin-like molecule from protozoan parasite Toxoplasma gondii that generates potent interleukin-12 (IL-12) murine DCs dependent on myeloid differentiation factor 88. T. profilin activates through...
Docosahexaenoic acid (DHA, C22:6) is highly enriched in brain, synapses, and retina a major omega-3 fatty acid. Deficiencies this essential are reportedly associated with neuronal function, cancer, inflammation. Here, using new lipidomic analyses employing high performance liquid chromatography coupled photodiode-array detector tandem mass spectrometer, novel series of endogenous mediators was identified blood, leukocytes, glial cells as 17S-hydroxy-containing docosanoids denoted...
The essential fatty acid eicosapentaenoic (EPA) present in fish oils displays beneficial effects a range of human disorders associated with inflammation including cardiovascular disease. Resolvin E1 (RvE1), new bioactive oxygenated product EPA, was identified plasma and prepared by total organic synthesis. Results bioaction physical matching studies indicate that the complete structure RvE1 is 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-EPA. At nanomolar levels, dramatically reduced dermal...
The endogenous cellular and molecular mechanisms that control acute inflammation its resolution are of wide interest. Using self-resolving inflammatory exudates lipidomics, we have identified a new pathway involving biosynthesis potent antiinflammatory proresolving mediators from the essential fatty acid docosahexaenoic (DHA) by macrophages (MΦs). During mouse peritonitis, accumulated both 17-hydroxydocosahexaenoic acid, known marker 17S-D series resolvin (Rv) protectin biosynthesis,...
Trihydroxytetraenes, a novel series of oxygenated derivatives formed from arachidonic acid in human leukocytes, were recently isolated [Serhan, C. N., Hamberg, M. & Samuelsson, B. (1984) Biochem. Biophys. Res. Commun. 118, 943-949]. The structure the major compound was established--i.e., 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid. present study reports second member trihydroxytetraene compounds--i.e., 5D,14,15L-trihydroxy-6,8,10,12-icosatetraenoic When added to neutrophils,...
Docosahexaenoic acid (DHA) is a lipid peroxidation target in oxidative injury to retinal pigment epithelium (RPE) and retina. Photoreceptor synaptic membranes share the highest content of DHA all cell membranes. This fatty required for RPE functional integrity; however, it not known whether specific mediators generated from contribute its biological significance. We used human ARPE-19 cells demonstrated synthesis 10,17 S -docosatriene [neuroprotectin D1 (NPD1)]. was enhanced by calcium...
Aspirin [acetylsalicylic acid (ASA)], along with its analgesic-antipyretic uses, is now also being considered for cardiovascular protection and treatments in cancer human immunodeficiency virus infection. Although many of ASA's pharmacological actions are related to ability inhibit prostaglandin thromboxane biosynthesis, some beneficial therapeutic effects not completely understood. Here, ASA triggered transcellular biosynthesis a previously unrecognized class eicosanoids during...
Endogenous mechanisms that act in the resolution of acute inflammation are essential for host defense and return to homeostasis. Resolvin D1 (RvD1), biosynthesized during resolution, displays potent stereoselective anti-inflammatory actions, such as limiting neutrophil infiltration proresolving actions. Here, we demonstrate RvD1 actions on human polymorphonuclear leukocytes (PMNs) pertussis toxin sensitive, decrease actin polymerization, block LTB 4 -regulated adhesion molecules (β2...
Abstract The cellular events underlying the resolution of acute inflammation are not known in molecular terms. To identify anti-inflammatory and proresolving circuits, we investigated temporal differential changes self-resolving murine exudates using mass spectrometry-based proteomics lipidomics. Key components were defined as indices including Ψmax, maximal neutrophil numbers that present during inflammatory response; Tmax, time when Ψmax occurs; interval (Ri) from Tmax to T50 reach half...