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

Jacinta P W Lee, Andrew Foote, Huapeng Fan, Celia Peral de Castro, Tali Lang, Sarah A. Jones, Nichita Gavrilescu, Kingston H G Mills, Michelle Leech, Eric F. Morand, James Harris

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)907 - 916
Number of pages10
JournalAutophagy
Volume12
Issue number6
DOIs
Publication statusPublished - 2 Jun 2016

Keywords

  • autophagosome
  • cytokines
  • inflammation
  • LPS
  • macrophage
  • reactive oxygen species
  • starvation

Cite this

Lee, Jacinta P W ; Foote, Andrew ; Fan, Huapeng ; Peral de Castro, Celia ; Lang, Tali ; Jones, Sarah A. ; Gavrilescu, Nichita ; Mills, Kingston H G ; Leech, Michelle ; Morand, Eric F. ; Harris, James. / Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages. In: Autophagy. 2016 ; Vol. 12, No. 6. pp. 907 - 916.
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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.",
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Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages. / Lee, Jacinta P W; Foote, Andrew; Fan, Huapeng; Peral de Castro, Celia; Lang, Tali; Jones, Sarah A.; Gavrilescu, Nichita; Mills, Kingston H G; Leech, Michelle; Morand, Eric F.; Harris, James.

In: Autophagy, Vol. 12, No. 6, 02.06.2016, p. 907 - 916.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Jones, Sarah A.

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