Apolipoprotein E deficiency and high-fat diet cooperate to trigger lipidosis and inflammation in the lung via the toll-like receptor 4 pathway
| Autor: | Huixia Lu, Ling Lin, Qiufang Ouyang, Huili Lin, Zhenhua Wang, Jingqin Ni, Ziyang Huang, Xiaoqing Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Apolipoprotein E
Male Cancer Research Lipidoses Biochemistry chemistry.chemical_compound Mice RNA Small Interfering Receptor Lung apolipoprotein E Mice Knockout Granuloma medicine.diagnostic_test NF-kappa B Articles medicine.anatomical_structure Cholesterol Oncology Molecular Medicine Cytokines lipids (amino acids peptides and proteins) medicine.symptom Bronchoalveolar Lavage Fluid Signal Transduction medicine.medical_specialty Inflammation Lung injury Biology Diet High-Fat Apolipoproteins E lipid Internal medicine Genetics medicine Animals Molecular Biology Pneumonia Mice Inbred C57BL Toll-Like Receptor 4 Bronchoalveolar lavage Endocrinology chemistry Gene Expression Regulation inflammation Myeloid Differentiation Factor 88 TLR4 toll-like receptor diet |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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