Critical Care: Mechanisms of Infections |

The Role of Interferon Regulatory Factor-1 on LPS-Induced ROS Production and Mitochondrial Damage in Macrophages FREE TO VIEW

Songyun Deng; Yuhang Ai; Lemeng Zhang; Pinhua Pan; Dongdong Wu
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Department of Intensive Care Unit, Xiangya Hospital, Changsha, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A182. doi:10.1016/j.chest.2016.02.188
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SESSION TITLE: Mechanisms of Infections

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, April 17, 2016 at 04:00 PM - 05:00 PM

PURPOSE: To investigate the role of interferon regulatory factor-1 (IRF-1) on lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production and mitochondrial damage in macrophages

METHODS:In vitro, stable overexpress or knockdown IRF-1 in murine macrophages RAW264.7 cells was by lentivirus expression vector transfection or lentivirus-mediated RNA interference (RNAi) transfection. The cells were stimulated with LPS (500ng/ml) for 16 hours and were for further study. In vivo, C57BL/6 wild type mice and IRF-1 knockout (KO) mice were randomly given intraperitoneal (IP) injections of PBS or LPS and were sacrificed 16 hours later. Peritoneal macrophages were isolated for further study. The mitochondrial membrane potential (△Ψm) was determined with JC-1; reactive oxygen species (ROS) was measured by DCFH-DA; intracellular ATP, SOD and MDA content were assayed by a commercial kit; Mitochondrial structure damage was also observed by transmission electron microscopy.

RESULTS:In vitro, LPS can induce ROS production, ATP depletion, SOD consumption, MDA accumulation and mitochondrial depolarization both in a time-dependent manner and dose-dependent manner. Following LPS stimulation, the ROS production was significantly reduced; mitochondrial depolarization and mitochondrial structure damage were significantly alleviated in IRF-1 knockdown cells. Moreover, IRF-1 knockdown can significantly alleviate LPS induced ATP depletion, SOD consumption and MDA accumulation. In contrast, IRF-1 overexpression can increase LPS induced ROS production, ATP depletion, SOD consumption, MDA accumulation and mitochondrial damage. In vivo, peritoneal macrophages obtained from IRF-1 KO mice demonstrate significantly decreased ROS production, mitochondrial depolarization and mitochondrial structure damage.

CONCLUSIONS: IRF-1 engages in LPS induced ROS production and mitochondrial damage in macrophages.

CLINICAL IMPLICATIONS: As ROS production and mitochondrial damage play a important role in sepsis, our research may prove a new clue for the therapy of sepsis.

DISCLOSURE: The following authors have nothing to disclose: Songyun Deng, Yuhang Ai, Lemeng Zhang, Pinhua Pan, Dongdong Wu

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