Open AccessA Cytosolic Phospholipase A2-Initiated Lipid Mediator Pathway Induces Autophagy in Macrophages
Author(s) -
Haiyan Qi,
Mathew P. Daniels,
Yueqin Liu,
Liyuan Chen,
Sara Alsaaty,
Stewart J. Levine,
James H. Shelhamer
Publication year - 2011
Publication title -
the journal of immunology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.1004004
Subject(s) - autophagy , lipid signaling , atg5 , microbiology and biotechnology , mediator , pi3k/akt/mtor pathway , biology , innate immune system , crosstalk , proinflammatory cytokine , lipid droplet , lipid metabolism , signal transduction , inflammation , cytosol , phospholipase a2 , chemistry , immune system , apoptosis , biochemistry , immunology , enzyme , physics , optics
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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom