Protective effects of peroxiredoxin 6 in modeling proinflammatory response using RAW 264.7 macrophages

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Abstract

The aim of the work was to study the effects of peroxiredoxin 6 (PRDX6), a recombinant antioxidant protein, on the level of proinflammatory responses caused by endotoxin exposure to RAW 264.7 macrophages. The addition of LPS to the RAW 264.7 cell culture medium expectedly increased the production of TNF-α, and the addition of PRDX6 led to a significant decrease in its production by 15-20%. The level of production of another proinflammatory cytokine, IL-1β, significantly activated by endotoxin, was completely normalized under the PRDX6 action. In addition, the addition of PRDX6 reduced the production of reactive oxygen species (ROS) induced by endotoxin and also prevented overexpression of the iNos gene in RAW 264.7 cells. The results showed that PRDX6 has a suppressive effect on the expression of the Nfe2l2 gene and the production of the transcription factor NRF-2 during the first 6 h of cell culture. The addition of endotoxin causes the activation of the NF-κB and SAPK/JNK signaling cascades, while in the presence of PRDX6, the activity of these signaling cascades decreases. It is known that the proinflammatory response of cells caused by bacterial LPS leads to the activation of apoptosis and the elimination of damaged cells. Our studies confirm this, since LPS leads to the activation of the Trp53 gene, a marker of apoptosis. The addition of peroxiredoxin 6 in the first hours of the development of an acute proinflammatory response leads to the suppression of Trp53 gene expression, which indicates a protective effect of PRDX6 that reduces apoptosis in RAW 264.7 macrophages.

About the authors

S. B Parfenyuk

Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences

Email: lana_kras2@rambler.ru
142290 Pushchino, Moscow Region, Russia

O. V Glushkova

Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences

142290 Pushchino, Moscow Region, Russia

M. G Sharapov

Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences

142290 Pushchino, Moscow Region, Russia

M. O Khrenov

Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences

142290 Pushchino, Moscow Region, Russia

S. M Lunin

Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences

142290 Pushchino, Moscow Region, Russia

A. A Kuzekova

Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences

142290 Pushchino, Moscow Region, Russia

E. K Mubarakshina

Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences

142290 Pushchino, Moscow Region, Russia

T. V Novoselova

Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences

142290 Pushchino, Moscow Region, Russia

D. A Cherenkov

Voronezh State University of Engineering Technologies

394036 Voronezh, Russia

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