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- Title
Cyclophilin D disruption attenuates lipopolysaccharide-induced inflammatory response in primary mouse macrophages.
- Authors
Priber, Janos; Fonai, Fruzsina; Jakus, Peter Balazs; Racz, Boglarka; Chinopoulos, Christos; Tretter, Laszlo; Gallyas, Ferenc; Sumegi, Balazs; Veres, Balazs
- 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.
- Subjects
CYCLOPHILINS; PHYSIOLOGICAL effects of lipopolysaccharides; IMMUNOREGULATION; NF-kappa B; PHOSPHORYLATION; MACROPHAGES; REACTIVE oxygen species; INFLAMMATION
- Publication
Biochemistry & Cell Biology, 2015, Vol 93, Issue 3, p241
- ISSN
0829-8211
- Publication type
Article
- DOI
10.1139/bcb-2014-0120