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Toll-like receptor 7 promotes the apoptosis of THP-1-derived macrophages through the CHOP-dependent pathway

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Macrophage apoptosis is a prominent characteristic of advanced atherosclerotic plaques and leads to plaque destabilization. Certain studies have confirmed that influenza virus A (IVA) infection is related to acute myocardial infarction (AMI). However, it remains unknown as to whether this phenomenon is associated with Toll-like receptor (TLR)7, since single-stranded RNA (ssRNA) of IVA is a natural ligand of TLR7. Thus, in the present study, THP-1derived macrophages were infected with IVA or treated with imiquimod (IMQ) in the presence or absence of pre-treatment with oxidized low-density lipoprotein (oxLDL). The macrophages were pre-treated with oxLDL (5 µg/ml) for 24 h to mimic high lipid conditions. Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-y-1)2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. Our results revealed that TLR7 played an important role in macrophage apoptosis and cytokine secretion. Both IVA infection and IMQ treatment increased TLR7 expression, as well as the secretion of pro-inflammatory cytokines [interleukin (IL)-6, monocyte chemotactic protein (MCP)-1] and apoptosis. However, this increase in cytokine secretion occurred independently of cell apoptosis. oxLDL had potential synergistic pro-apoptotic effects combined with TLR7 activation. To determine whether endoplasmic reticulum (ER) stress plays a role in cell apoptosis, the mRNA and protein expression of known markers of ER stress [glucose-regulated protein (GRP)78 and C/EBP homologous protein (CHOP)] was detected by reverse transcription PCR (RT-PCR), quantitative reverse transcription PCR (qRT-PCR) and western blot analysis. Our results revealed that apoptosis aggravated ER stress, as shown by the overexpression of the pro-apoptotic sensor, CHOP. In conclusion, our study demonstrates the converging role of oxLDL pre-treatment, IVA infection and IMQ in ER stress-induced cell apoptosis.
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Document Type: Research Article

Affiliations: Department of Laboratory Diagnostics, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China

Publication date: January 1, 2014

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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