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PMID: 27163877 Published · ppublish English Journal Article

Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages.

Autophagy ·Vol. 12 ·No. 6 ·2016-00-02 ·Pages 907-16

Lee JP, Foote A, Fan H, Peral de Castro C, Lang T, Jones SA, Gavrilescu N, Mills KH, Leech M, Morand EF, Harris J

Abstract

MIF (macrophage migration inhibitory factor [glycosylation-inhibiting factor]) is a pro-inflammatory cytokine expressed in multiple cells types, including macrophages. MIF plays a pathogenic role in a number of inflammatory diseases and has been linked to tumor progression in some cancers. Previous work has demonstrated that loss of autophagy in macrophages enhances secretion of IL1 family cytokines. Here, we demonstrate that loss of autophagy, by pharmacological inhibition or siRNA silencing of Atg5, enhances MIF secretion by monocytes and macrophages. We further demonstrate that this is dependent on mitochondrial reactive oxygen species (ROS). Induction of autophagy with MTOR inhibitors had no effect on MIF secretion, but amino acid starvation increased secretion. This was unaffected by Atg5 siRNA but was again dependent on mitochondrial ROS. Our data demonstrate that autophagic regulation of mitochondrial ROS plays a pivotal role in the regulation of inflammatory cytokine secretion in macrophages, with potential implications for the pathogenesis of inflammatory diseases and cancers.

Keywords
LPS autophagosome cytokines inflammation macrophage reactive oxygen species starvation
MeSH Terms
Amino Acids/deficiency Animals Autophagy Humans Macrophage Migration-Inhibitory Factors/metabolism Macrophages/metabolism Mice Mitochondria/metabolism RAW 264.7 Cells Reactive Oxygen Species/metabolism
Chemicals
Amino Acids Macrophage Migration-Inhibitory Factors Reactive Oxygen Species
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Lee Jacinta P W
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
Foote Andrew
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
Fan Huapeng
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
Peral de Castro Celia
b Immune Regulation Research Group, Department of Biochemistry and Immunology, Trinity College , Dublin , Ireland.
Lang Tali
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
Jones Sarah A
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
Gavrilescu Nichita
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
Mills Kingston H G
b Immune Regulation Research Group, Department of Biochemistry and Immunology, Trinity College , Dublin , Ireland.
Leech Michelle
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
Morand Eric F
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
Harris James
a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.
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Article Info
Journal
Autophagy
Abbr.
Autophagy
ISSN
1554-8635
DOI
10.1080/15548627.2016.1164358
Published
2016-00-02
Epub
2016-00-10
Pages
907-16
Language
English
Region
United States
NLM ID
101265188
PMCID
PMC4922441
Subset
IM
External Links
PubMed source DOI: 10.1080/15548627.2016.1164358 PMC Full Text View journal details
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