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

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
Janos PriberBalazs Veres

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 e...Continue Reading

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Citations

Oct 31, 2015·Scientific Reports·Michele TavecchioDario C Altieri
Jun 26, 2017·Biochemical and Biophysical Research Communications·Jennifer Rieusset
Dec 24, 2019·Expert Opinion on Investigational Drugs·Daren R UreRobert T Foster
Dec 13, 2017·Clinical and Experimental Pharmacology & Physiology·Weiping HouFrank Y Ma
Oct 9, 2020·International Journal of Molecular Sciences·Fadi H J RamadanZita Bognar
Aug 17, 2021·American Journal of Physiology. Renal Physiology·Hee-Seong JangBabu J Padanilam

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