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

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) stre...

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Autores principales:	Mohammad Saeed Hakhamaneshi, Alina Abdolahi, Zakaria Vahabzadeh, Mohammad Abdi, Pedram Andalibi
Formato:	article
Lenguaje:	EN
Publicado:	Royan Institute (ACECR), Tehran 2021
Materias:	macrophage toll-like receptor 4 trimethylamine-n-oxide Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77a627ec1ccf43e58073c821d0a7c038
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spelling	oai:doaj.org-article:77a627ec1ccf43e58073c821d0a7c0382021-11-07T07:06:39ZToll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide10.22074/cellj.2021.78492228-58062228-5814https://doaj.org/article/77a627ec1ccf43e58073c821d0a7c0382021-10-01T00:00:00Zhttps://celljournal.org/journal/article/fulltext/toll-like-receptor-4-a-macrophage-cell-surface-receptor-is-activated-by-trimethylamine-n-oxide-during-atherosclerosis.pdfhttps://doaj.org/toc/2228-5806https://doaj.org/toc/2228-5814Objective: 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 μM) 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 2μg/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 μM 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.Mohammad Saeed HakhamaneshiAlina AbdolahiZakaria VahabzadehMohammad AbdiPedram AndalibiRoyan Institute (ACECR), Tehranarticlemacrophagetoll-like receptor 4trimethylamine-n-oxideMedicineRScienceQENCell Journal, Vol 23, Iss 5, Pp 516-522 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	macrophage toll-like receptor 4 trimethylamine-n-oxide Medicine R Science Q
spellingShingle	macrophage toll-like receptor 4 trimethylamine-n-oxide Medicine R Science Q Mohammad Saeed Hakhamaneshi Alina Abdolahi Zakaria Vahabzadeh Mohammad Abdi Pedram Andalibi Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide
description	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 μM) 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 2μg/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 μM 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.
format	article
author	Mohammad Saeed Hakhamaneshi Alina Abdolahi Zakaria Vahabzadeh Mohammad Abdi Pedram Andalibi
author_facet	Mohammad Saeed Hakhamaneshi Alina Abdolahi Zakaria Vahabzadeh Mohammad Abdi Pedram Andalibi
author_sort	Mohammad Saeed Hakhamaneshi
title	Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide
title_short	Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide
title_full	Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide
title_fullStr	Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide
title_full_unstemmed	Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide
title_sort	toll-like receptor 4: a macrophage cell surface receptor is activated by trimethylamine-n-oxide
publisher	Royan Institute (ACECR), Tehran
publishDate	2021
url	https://doaj.org/article/77a627ec1ccf43e58073c821d0a7c038
work_keys_str_mv	AT mohammadsaeedhakhamaneshi tolllikereceptor4amacrophagecellsurfacereceptorisactivatedbytrimethylaminenoxide AT alinaabdolahi tolllikereceptor4amacrophagecellsurfacereceptorisactivatedbytrimethylaminenoxide AT zakariavahabzadeh tolllikereceptor4amacrophagecellsurfacereceptorisactivatedbytrimethylaminenoxide AT mohammadabdi tolllikereceptor4amacrophagecellsurfacereceptorisactivatedbytrimethylaminenoxide AT pedramandalibi tolllikereceptor4amacrophagecellsurfacereceptorisactivatedbytrimethylaminenoxide
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Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide

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