Fusaric acid induces NRF2 as a cytoprotective response to prevent NLRP3 activation in the liver derived HepG2 cell line.

Naeem Sheik Abdul, Savania Nagiah, Anil A Chuturgoon

Journal: Toxicology in vitro : an international journal published in association with BIBRA 2019;55():151-159

PMID: 30582969

Full Text on Elsevier Science View on PubMed

Abstract

Fusaric acid (FA) is a neglected fusarium mycotoxin despite its ubiquitous presence. FA is a niacin related compound and mediates toxicity via oxidative stress and mitochondrial dysfunction. The NLRP3 inflammasome is a multiprotein scaffold that plays a key role in IL-β maturation. We investigated the effects of FA on IL-1β processing, NRLP3 inflammasome priming and activation along with the potential of FA to initiate cytoprotective mechanisms using spectrophotometry, luminometry, qPCR and western blots in the HepG2 liver cell line. FA disrupted synthesis and maturation of IL-1β by inhibiting NRLP3 priming and activation. Further experimentation revealed an up-regulation of NRF2 with concomitant elevation in the anti-oxidant enzyme SOD2 and autophagy markers suggesting that FA induces NRF2 cytoprotective programs in these cells. We conclude that FA attenuates inflammasome priming and activation and sheds light on the immunosuppressive potential of FA in liver cells.

Address: Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.; Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa. Electronic address: [email protected].

DOI: 10.1016/j.tiv.2018.12.008

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MeSH Terms: Fusaric Acid, Hep G2 Cells, Humans, Interleukin-1beta, Liver, NF-E2-Related Factor 2, NLR Family, Pyrin Domain-Containing 3 Protein, Superoxide Dismutase