Open Access

Mitochondrial DNA induces inflammation and increases TLR9/NF-κB expression in lung tissue

  • Authors:
    • Jian-Zheng Zhang
    • Zhi Liu
    • Jia Liu
    • Ji-Xin Ren
    • Tian-Sheng Sun
  • View Affiliations

  • Published online on: February 10, 2014     https://doi.org/10.3892/ijmm.2014.1650
  • Pages: 817-824
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Mitochondrial DNA (mtDNA) contains unmethylated CpG motifs that exhibit immune stimulatory capacities. The aim of this study was to investigate whether mtDNA activates the Toll-like receptor 9 (TLR9)/nuclear factor-κB (NF-κB) pathway, thereby contributing to post-traumatic systemic inflammatory response syndrome (SIRS) and lung injury in rats. The effects of mtDNA on macrophage culture were examined in order to elucidate the putative cellular mechanisms. Rats and macrophage cultures were treated with phosphate-buffered saline, nuclear DNA, or mtDNA for 2, 4, 8 and 24 h. Histological analysis of lung tissue was undertaken following hematoxylin and eosin staining, and cytokine levels were assessed by ELISA. NF-κB and IκB-α phosphorylation levels, as well as TLR9 protein expression were determined by western blot analysis; NF-κB, IκB-α and TLR9 mRNA levels were analyzed by RT-PCR. A greater degree of inflammation and lung injury was observed in response to mtDNA. In addition, mtDNA increased serum tumor necrosis factor-α, interleukin (IL)-6 and IL-10 levels in vivo and increased their secretion by cultured macrophages (p<0.05). In lung tissue, mtDNA increased NF-κB, IκB-α and TLR9 mRNA levels (p<0.05); it also increased phosphorylated NF-κB p65 and TLR9 protein levels in the macrophage cultures. Thus, mtDNA may be part of the danger-associated molecular patterns, contributing to the initiation of sterile SIRS through the activation of the TLR9/NF-κB pathway and the induction of pro-inflammatory cytokine production.
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2014-April
Volume 33 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Zhang, J., Liu, Z., Liu, J., Ren, J., & Sun, T. (2014). Mitochondrial DNA induces inflammation and increases TLR9/NF-κB expression in lung tissue. International Journal of Molecular Medicine, 33, 817-824. https://doi.org/10.3892/ijmm.2014.1650
MLA
Zhang, J., Liu, Z., Liu, J., Ren, J., Sun, T."Mitochondrial DNA induces inflammation and increases TLR9/NF-κB expression in lung tissue". International Journal of Molecular Medicine 33.4 (2014): 817-824.
Chicago
Zhang, J., Liu, Z., Liu, J., Ren, J., Sun, T."Mitochondrial DNA induces inflammation and increases TLR9/NF-κB expression in lung tissue". International Journal of Molecular Medicine 33, no. 4 (2014): 817-824. https://doi.org/10.3892/ijmm.2014.1650