Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B 4 synthesis by inhibiting a calcium-activated kinase pathway
Copyright policy )Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B 4 synthesis by inhibiting a calcium-activated kinase pathway
Significance Specialized proresolving mediators, such as resolvin D1 (RvD1), are endogenous molecules that both dampen inflammation without compromising host defense and promote tissue resolution. A prime example is RvD1’s ability to decrease the ratio of proinflammatory leukotriene B 4 (LTB 4 ) to proresolving lipoxin A 4 (LXA 4 ), but the mechanism is not known. We have discovered a new calcium kinase signaling pathway through which RvD1 lowers the nuclear:cytoplasmic ratio of 5-lipoxygenase (5-LOX), the common enzyme for LTB 4 and LXA 4 biosynthesis This shift in 5-LOX localization dampens LTB 4 production and enhances LXA 4 production. By providing a new mechanistic understanding of how RvD1 tempers inflammation to facilitate resolution, these findings can help devise new therapeutic strategies for diseases driven by nonresolving inflammation.
- King’s University United States
- Columbia University United States
- Deutsche Zentren der Gesundheitsforschung Germany
- Heidelberg University Germany
- University of Louisville United States
Cell Nucleus, Mice, Knockout, Cytoplasm, Arachidonate 5-Lipoxygenase, Arachidonic Acid, Microscopy, Confocal, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Macrophages, Immunoblotting, Intracellular Signaling Peptides and Proteins, Mice, Transgenic, Leukotriene B4, Mice, Inbred C57BL, Animals, Calcium, Female, Phosphorylation, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cells, Cultured
Cell Nucleus, Mice, Knockout, Cytoplasm, Arachidonate 5-Lipoxygenase, Arachidonic Acid, Microscopy, Confocal, Docosahexaenoic Acids, Dose-Response Relationship, Drug, Macrophages, Immunoblotting, Intracellular Signaling Peptides and Proteins, Mice, Transgenic, Leukotriene B4, Mice, Inbred C57BL, Animals, Calcium, Female, Phosphorylation, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cells, Cultured
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