Cyclophilin D disruption attenuates lipopolysaccharide-induced inflammatory response in primary mouse macrophages

Janos Priber, Fruzsina Fonai, Peter Balazs Jakus, Boglarka Racz, Christos Chinopoulos, Laszlo Tretter, Ferenc Gallyas, Balazs Sumegi, Balazs Veres

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

According to recent results, various mitochondrial processes can actively regulate the immune response. In the present report, we studied whether mitochondrial permeability transition (mPT) has such a role. To this end, we compared bacterial lipopolysaccharide (LPS)-induced inflammatory response in cyclophilin D (CypD) knock-out and wild-type mouse resident peritoneal macrophages. CypD is a regulator of mPT; therefore, mPT is damaged in CypD-/- cells. We chose this genetic modification-based model because the mPT inhibitor cyclosporine A regulates inflammatory processes by several pathways unrelated to the mitochondria. The LPS increased mitochondrial depolarisation, cellular and mitochondrial reactive oxygen species production, nuclear factor-κB activation, and nitrite-and tumour necrosis factor α accumulation in wild-type cells, but these changes were diminished or absent in the CypD-deficient macrophages. Additionally, LPS enhanced Akt phosphorylation/activation as well as FOXO1 and FOXO3a phosphorylation/inactivation both in wild-type and CypD-/- cells. However, Akt and FOXO phosphorylation was significantly more pronounced in CypD-deficient compared to wild-type macrophages. These results provide the first pieces of experimental evidence for the functional regulatory role of mPT in the LPS-induced early inflammatory response of macrophages.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalBiochemistry and Cell Biology
Volume93
Issue number3
DOIs
Publication statusPublished - Jan 23 2015

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Keywords

  • Cyclophilin D disruption
  • Mitochondrial permeability transition
  • Nuclear factor-κB
  • Peritoneal macrophages
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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