Macrophage migration inhibitory factor induces autophagy via reactive oxygen species generation

Yung Chun Chuang, Wen Hong Su, Huan Yao Lei, Yee-Shin Lin, Hsiao-Sheng Liu, Chih-Peng Chang, Trai-Ming Yeh

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Autophagy is an evolutionarily conserved catabolic process that maintains cellular homeostasis under stress conditions such as starvation and pathogen infection. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that plays important roles in inflammation and tumorigenesis. Cytokines such as IL-1β and TNF-α that are induced by MIF have been shown to be involved in the induction of autophagy. However, the actual role of MIF in autophagy remains unclear. Here, we have demonstrated that incubation of human hepatoma cell line HuH-7 cells with recombinant MIF (rMIF) induced reactive oxygen species (ROS) production and autophagy formation, including LC3-II expression, LC3 punctae formation, autophagic flux, and mitochondria membrane potential loss. The autophagy induced by rMIF was inhibited in the presence of MIF inhibitor, ISO-1 as well as ROS scavenger N-acetyl-L-cysteine (NAC). In addition, serum starvation-induced MIF release and autophagy of HuH-7 cells were partly blocked in the presence of NAC. Moreover, diminished MIF expression by shRNA transfection or inhibition of MIF by ISO-1 decreased serum starvation-induced autophagy of HuH-7 cells. Taken together, these data suggest that cell autophagy was induced by MIF under stress conditions such as inflammation and starvation through ROS generation.

Original languageEnglish
Article numbere37613
JournalPloS one
Volume7
Issue number5
DOIs
Publication statusPublished - 2012 May 22

Fingerprint

Macrophage Migration-Inhibitory Factors
autophagy
Autophagy
reactive oxygen species
Reactive Oxygen Species
Acetylcysteine
Starvation
Cytokines
starvation
Mitochondria
Pathogens
Interleukin-1
acetylcysteine
Small Interfering RNA
Cells
Fluxes
Membranes
cytokines
inflammation
cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "Macrophage migration inhibitory factor induces autophagy via reactive oxygen species generation",
abstract = "Autophagy is an evolutionarily conserved catabolic process that maintains cellular homeostasis under stress conditions such as starvation and pathogen infection. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that plays important roles in inflammation and tumorigenesis. Cytokines such as IL-1β and TNF-α that are induced by MIF have been shown to be involved in the induction of autophagy. However, the actual role of MIF in autophagy remains unclear. Here, we have demonstrated that incubation of human hepatoma cell line HuH-7 cells with recombinant MIF (rMIF) induced reactive oxygen species (ROS) production and autophagy formation, including LC3-II expression, LC3 punctae formation, autophagic flux, and mitochondria membrane potential loss. The autophagy induced by rMIF was inhibited in the presence of MIF inhibitor, ISO-1 as well as ROS scavenger N-acetyl-L-cysteine (NAC). In addition, serum starvation-induced MIF release and autophagy of HuH-7 cells were partly blocked in the presence of NAC. Moreover, diminished MIF expression by shRNA transfection or inhibition of MIF by ISO-1 decreased serum starvation-induced autophagy of HuH-7 cells. Taken together, these data suggest that cell autophagy was induced by MIF under stress conditions such as inflammation and starvation through ROS generation.",
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Macrophage migration inhibitory factor induces autophagy via reactive oxygen species generation. / Chuang, Yung Chun; Su, Wen Hong; Lei, Huan Yao; Lin, Yee-Shin; Liu, Hsiao-Sheng; Chang, Chih-Peng; Yeh, Trai-Ming.

In: PloS one, Vol. 7, No. 5, e37613, 22.05.2012.

Research output: Contribution to journalArticle

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AU - Chuang, Yung Chun

AU - Su, Wen Hong

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AU - Chang, Chih-Peng

AU - Yeh, Trai-Ming

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