Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells

Abstract Fusaric acid (FA), a food-borne mycotoxin, is a potent divalent metal chelator. The human immune system is complex and susceptible to environmental insult however, the immunotoxity of FA remains unknown. We investigated the immunotoxicity of FA on human peripheral blood mononuclear cells (P...

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Autores principales: Shanel Dhani, Savania Nagiah, Dhaneshree B. Naidoo, Anil A. Chuturgoon
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/06c39d183cc1470a98a5a2a5e327538d
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spelling oai:doaj.org-article:06c39d183cc1470a98a5a2a5e327538d2021-12-02T11:53:06ZFusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells10.1038/s41598-017-03183-02045-2322https://doaj.org/article/06c39d183cc1470a98a5a2a5e327538d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03183-0https://doaj.org/toc/2045-2322Abstract Fusaric acid (FA), a food-borne mycotoxin, is a potent divalent metal chelator. The human immune system is complex and susceptible to environmental insult however, the immunotoxity of FA remains unknown. We investigated the immunotoxicity of FA on human peripheral blood mononuclear cells (PBMCs) and Thp-1 cells. FA was cytotoxic to PBMCs (IC50-240.8 μg/ml) and Thp-1 (IC50-107.7 μg/ml) cells at 24 h. FA induced early apoptosis but significantly decreased caspase activity in PBMCs, a characteristic of paraptosis. In Thp-1 cells, FA induced apoptosis and increased caspase −9 and −3/7 activities. In PBMCs, FA maintained mitochondrial membrane potential and decreased protein expression of Bax whilst increasing expression of p-Bcl-2; FA induced oxidative stress and depleted ATP levels in both cell types. In Thp-1 cells, FA increased mitochondrial membrane depolarization and decreased p-Bcl-2 expression. In PBMCs, FA significantly up-regulated the MAPK protein expression of p-ERK and p-JNK but down-regulated p-p38 expression. In Thp-1 cells, FA up-regulated MAPK protein expression of p-ERK whilst p-JNK and p-p38 expression were down-regulated. In conclusion FA induced programmed cell death and altered MAPK signaling in healthy PBMCs and Thp-1 cells strongly suggesting a possible mechanism of FA induced immunotoxicity in vitro.Shanel DhaniSavania NagiahDhaneshree B. NaidooAnil A. ChuturgoonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shanel Dhani
Savania Nagiah
Dhaneshree B. Naidoo
Anil A. Chuturgoon
Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells
description Abstract Fusaric acid (FA), a food-borne mycotoxin, is a potent divalent metal chelator. The human immune system is complex and susceptible to environmental insult however, the immunotoxity of FA remains unknown. We investigated the immunotoxicity of FA on human peripheral blood mononuclear cells (PBMCs) and Thp-1 cells. FA was cytotoxic to PBMCs (IC50-240.8 μg/ml) and Thp-1 (IC50-107.7 μg/ml) cells at 24 h. FA induced early apoptosis but significantly decreased caspase activity in PBMCs, a characteristic of paraptosis. In Thp-1 cells, FA induced apoptosis and increased caspase −9 and −3/7 activities. In PBMCs, FA maintained mitochondrial membrane potential and decreased protein expression of Bax whilst increasing expression of p-Bcl-2; FA induced oxidative stress and depleted ATP levels in both cell types. In Thp-1 cells, FA increased mitochondrial membrane depolarization and decreased p-Bcl-2 expression. In PBMCs, FA significantly up-regulated the MAPK protein expression of p-ERK and p-JNK but down-regulated p-p38 expression. In Thp-1 cells, FA up-regulated MAPK protein expression of p-ERK whilst p-JNK and p-p38 expression were down-regulated. In conclusion FA induced programmed cell death and altered MAPK signaling in healthy PBMCs and Thp-1 cells strongly suggesting a possible mechanism of FA induced immunotoxicity in vitro.
format article
author Shanel Dhani
Savania Nagiah
Dhaneshree B. Naidoo
Anil A. Chuturgoon
author_facet Shanel Dhani
Savania Nagiah
Dhaneshree B. Naidoo
Anil A. Chuturgoon
author_sort Shanel Dhani
title Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells
title_short Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells
title_full Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells
title_fullStr Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells
title_full_unstemmed Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells
title_sort fusaric acid immunotoxicity and mapk activation in normal peripheral blood mononuclear cells and thp-1 cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/06c39d183cc1470a98a5a2a5e327538d
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