Repository of Research and Investigative Information

Repository of Research and Investigative Information

Kurdistan University of Medical Sciences

Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated By Trimethylamine-N-Oxide

(2021) Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated By Trimethylamine-N-Oxide. Cell journal.

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OBJECTIVE: Trimethylamine-N-Oxide (TMAO) is considered as a risk factor for atherosclerosis which further leads to inflammation during atherosclerosis. The exact mechanism(s) by which TMAO induces the inflammatory reactions remains to be determined. TMAO can cause the endoplasmic reticulum (ER) stress that triggers activation of Toll-Like Receptors (TLRs). In macrophages, this process stimulates the production of proinflammatory cytokines. This study designed to evaluate the expression level of TLR4 in TMAO-treated macrophages. MATERIALS AND METHODS: In this experimental study, different concentrations of TMAO (37.5, 75, 150, and 300 muM) were exposed to murine macrophage (J774A.1 cell line) for 8, 18, 24, and 48 hours. The cells were also treated with 2.5 mM of 4-phenyl butyric acid as well as 2mug/ml of tunicamycin respectively as negative and positive controls for inducing ER-stress. We measured the viability of treated cells by the MTT test. Besides, the expression levels of TLR4 gene and protein were evaluated using western blotting and reverse transcription- quantitative polymerase chain reaction (RT-qPCR) analysis. One-Way ANOVA was used for statistical analysis. RESULTS: No cell death was observed in treated cells. The cells treated with 150 and 300 muM doses of TMAO for 24 hours showed a significant elevation in the protein and/or mRNA levels of TLR4 when compared to normal control or tunicamycin-treated cells. CONCLUSION: Our results may in part elucidate the mechanism by which TMAO induces the macrophage inflammatory reactions in response to the induction of ER stress, similar to what happens during atherosclerosis. It also provides documentation to support the direct contribution of TLR4 in TMAO-induced inflammation.

Item Type: Article
Keywords: Macrophage Trimethylamine-N-Oxide Toll-Like Receptor 4
Page Range: pp. 516-522
Journal or Publication Title: Cell journal
Volume: 23
Number: 5
Depositing User: مهندس مهدی شریفی

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