Critical Care: Critical Care: Sepsis |

LPS-Induced Mitochondrial DNA Release Causes Acute Lung Injury and Systemic Inflammation Through Toll-like Receptor 9 in Mice 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):A168. doi:10.1016/j.chest.2016.02.174
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SESSION TITLE: Critical Care: Sepsis

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: To investigate the role of mitochondrial DNA (mtDNA) release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation.

METHODS: Wild type C57BL/6 mice and matched toll-like receptor 4 (TLR4) KO mice were randomly assigned to sham and LPS groups. LPS/PBS were given by intraperitoneal (IP) injection. The mice were sacrificed 16 hours after LPS injection and plasma were isolated for mtDNA detection by Q-PCR. Furthermore, C57BL/6 mice were randomly assigned to ODN 2088 control and ODN2088 group pretreated 1h before mtDNA injection; all the mice were sacrificed 16 hours later. Lungs were harvested for HE staining; and were for BALF total protein concentration and lung W/D ratio analyse. Serum levels of IL-1 beta, IL-6, HMGB1 were measured by ELISA kit.

RESULTS: Following LPS treatment, plasma mtDNA copies in TLR4 KO mice were significantly decreased compared toC57BL/6 mice. After the treatment of mtDNA, the TLR4 KO group, sham group and ODN 2088 control group showed no significant differences on the lung injury score, lung wet/dry ratio, BALF total protein concentration and serum IL-1, IL-6 and HMGB1 levels. Compared to ODN 2088 control group, ODN 2088 (specific TLR9 inhibitor) pretreatment can significantly attenuate lung injury score, decrease lung wet/dry ratio, BALF total protein concentration, and decrease the level of IL-1beta, IL-6 and HMGB1 in serum.

CONCLUSIONS: LPS induced mtDNA release occurs in a TLR4 dependent manner. And mtDNA causes acute lung injury and systemic inflammation in a TLR9 dependent manner.

CLINICAL IMPLICATIONS: Our research demonstrates that LPS induced mtDNA release can cause lung injury and systemic inflammation, it suggests that maybe we can use TLR4 or TLR9 inhibitor 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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