Effect of interferon regulatory factor 2 on inflammatory response and oxidative stress in lipopolysaccharide-induced acute kidney injury.

Autor: He T; Department of Nephrology, The Yantai Yuhuangding Hospital, Yantai, China., Yang L; Department of Nephrology, The Yantai Yuhuangding Hospital, Yantai, China., Wu D; Department of Nephrology, The Yantai Yuhuangding Hospital, Yantai, China.
Jazyk: angličtina
Zdroj: Drug development research [Drug Dev Res] 2022 Jun; Vol. 83 (4), pp. 940-951. Date of Electronic Publication: 2022 Jan 28.
DOI: 10.1002/ddr.21919
Abstrakt: Interferon regulatory factor (IRF) 2 plays an important role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). In this study, we explored the effects of IRF2 on apoptosis, inflammation, and oxidative stress in AKI C57BL/6 male mouse model and HEK293 cells following LPS treatment. To determine the effect of IRF2, short hairpin RNAs in mice and small interfering RNAs in cells were used to knockdown IRF2 expression. IRF2 expression, apoptosis, and severity of inflammatory and oxidative stress in mice and cells were measured. IRF2 levels were upregulated in LPS-treated mice and cells. IRF2 knockdown suppressed the levels of creatinine, blood urea nitrogen, and kidney injury molecule 1 and decreased the renal injury score in mice. Furthermore, IRF2 knockdown inhibited apoptosis and decreased the levels of inflammatory, reactive oxygen species (ROS), and malondialdehyde (MDA), but increased superoxide dismutase (SOD) levels in mice and cells. Furthermore, we found that the Janus kinase (JAK)/ signal transducer and activator of transcription pathway activated by LPS was inhibited by knockdown of IRF2, and enhanced by IRF2 overexpression. IRF2 overexpression increased cell apoptosis, inflammation, and ROS and MDA levels, and decreased SOD levels. However, the effect of IRF2 overexpression was reversed by the JAK inhibitor tofacitinib. Knockdown of IRF2 reduced LPS-induced renal tissue injury in vivo and in vitro through anti-inflammatory and antioxidant stress effects.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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