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Apolipoprotein E deficiency and high‑fat diet cooperate to trigger lipidosis and inflammation in the lung via the toll-like receptor 4 pathway

  • Authors:
    • Qiufang Ouyang
    • Ziyang Huang
    • Huili Lin
    • Jingqin Ni
    • Huixia Lu
    • Xiaoqing Chen
    • Zhenhua Wang
    • Ling Lin

  • View Affiliations

  • Published online on: May 12, 2015     https://doi.org/10.3892/mmr.2015.3774
  • Pages: 2589-2597

  • Copyright: © Ouyang 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

Apolipoprotein E deficiency (ApoE‑/‑) combined with a high‑fat Western‑type diet (WD) is known to activate the toll‑like receptor (TLR4) pathway and promote atherosclerosis. However, to date, the pathogenic effects of these conditions on the lung have not been extensively studied. Therefore, the present study examined the effects of ApoE‑/‑ and a WD on lung injury and investigated the underlying mechanisms. ApoE‑/‑ and wild‑type mice were fed a WD or normal chow diet for 4, 12 and 24 weeks. Lung inflammation, lung cholesterol content and cytokines profiles in broncho‑alveolar lavage fluid (BALF) were determined. TLR4 and its main downstream molecules were analyzed with western blot analysis. In addition, the role of the TLR4 pathway was further validated using TLR4‑targeted gene silencing. The results showed that ApoE‑/‑ mice developed lung lipidosis following 12 weeks of receiving a WD, as evidenced by an increased lung cholesterol content. Moreover, dependent on the time period of receiving the diet, those mice exhibited pulmonary inflammation, which was manifested by initial leukocyte recruitment (at 4 weeks), by increased alveolar septal thickness and mean linear intercept as well as elevated production of inflammation mediators (at 12 weeks), and by granuloma formation (at 24 weeks). The expression levels of TLR4, myeloid differentiation primary response 88 (MyD88) and nuclear factor kappa B were markedly upregulated in ApoE‑/‑ WD mice at week 12. However, these effects were ameliorated by shRNA‑mediated knockdown of TLR4. By contrast, ApoE‑/‑ ND or wild‑type WD mice exhibited low‑grade or no inflammation and mild lipidosis. The levels of TLR4 and MyD88 in those mice showed only minor changes. In conclusion, ApoE deficiency acts synergistically with a WD to trigger lung lipidosis and inflammation at least in part via TLR4 signaling.
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August-2015
Volume 12 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ouyang Q, Huang Z, Lin H, Ni J, Lu H, Chen X, Wang Z and Lin L: Apolipoprotein E deficiency and high‑fat diet cooperate to trigger lipidosis and inflammation in the lung via the toll-like receptor 4 pathway. Mol Med Rep 12: 2589-2597, 2015.
APA
Ouyang, Q., Huang, Z., Lin, H., Ni, J., Lu, H., Chen, X. ... Lin, L. (2015). Apolipoprotein E deficiency and high‑fat diet cooperate to trigger lipidosis and inflammation in the lung via the toll-like receptor 4 pathway. Molecular Medicine Reports, 12, 2589-2597. https://doi.org/10.3892/mmr.2015.3774
MLA
Ouyang, Q., Huang, Z., Lin, H., Ni, J., Lu, H., Chen, X., Wang, Z., Lin, L."Apolipoprotein E deficiency and high‑fat diet cooperate to trigger lipidosis and inflammation in the lung via the toll-like receptor 4 pathway". Molecular Medicine Reports 12.2 (2015): 2589-2597.
Chicago
Ouyang, Q., Huang, Z., Lin, H., Ni, J., Lu, H., Chen, X., Wang, Z., Lin, L."Apolipoprotein E deficiency and high‑fat diet cooperate to trigger lipidosis and inflammation in the lung via the toll-like receptor 4 pathway". Molecular Medicine Reports 12, no. 2 (2015): 2589-2597. https://doi.org/10.3892/mmr.2015.3774