title: A cytosolic phospholipase A2-initiated lipid mediator pathway induces autophagy in macrophages.
abstract: Autophagy delivers cytoplasmic constituents to autophagosomes and is involved in innate and adaptive immunity. Cytosolic phospholipase (cPLA(2))-initiated proinflammatory lipid mediator pathways play a critical role in host defense and inflammation. The crosstalk between the two pathways remains unclear. In this study, we report that cPLA(2) and its metabolite lipid mediators induced autophagy in the RAW246.7 macrophage cell line and in primary monocytes. IFN-γ-triggered autophagy involves activation of cPLA(2). Cysteinyl leukotrienes D(4) and E(4) and PGD(2) also induced these effects. The autophagy is independent of changes in mTOR or autophagic flux. cPLA(2) and lipid mediator-induced autophagy is ATG5 dependent. These data suggest that lipid mediators play a role in the regulation of autophagy, demonstrating a connection between the two seemingly separate innate immune responses, induction of autophagy and lipid mediator generation.
authors: Critical Care Medicine Department, Clinical Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Hai-Yan
authors: HY
authors: Qi
authors: Mathew P
authors: MP
authors: Daniels
authors: Yueqin
authors: Y
authors: Liu
authors: Li-Yuan
authors: LY
authors: Chen
authors: Sara
authors: S
authors: Alsaaty
authors: Stewart J
authors: SJ
authors: Levine
authors: James H
authors: JH
authors: Shelhamer
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D015777:Eicosanoids / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D050356:Lipid Metabolism / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D054510:Phospholipases A2, Cytosolic / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D015777:Eicosanoids; D018836:Inflammation Mediators; D054510:Phospholipases A2, Cytosolic