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Author El Ali, Zeina
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ALLERGY ♦ APOPTOSIS ♦ BENZOQUINONES ♦ BONE MARROW ♦ BORON CHLORIDES ♦ DENDRITES ♦ DERMATITIS ♦ ECR HEATING ♦ GENES ♦ GLUTATHIONE ♦ HEME ♦ MICE ♦ MONOCYTES ♦ NITRIC OXIDE ♦ OXYGENASES ♦ PEROXIDASES ♦ PHOSPHOTRANSFERASES ♦ SENSITIZERS ♦ SKELETON
Abstract Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action. First, we performed a RT-qPCR array showing that CinA was a higher inducer of immune and detoxification genes compared to DNCB. Interestingly, in the absence of Nrf2, gene expression was dramatically affected in response to DNCB but was slightly affected in response to CinA. These observations prompted us to study DC's cell death in response to both chemicals. DNCB and CinA increased apoptotic cells and decreased living cells in the absence of Nrf2. The characterization of DC apoptosis induced by both CS involved the mitochondrial-dependent caspase pathway and was regulated via Nrf2 in response to both chemicals. Oxidative stress induced by DNCB, and leading to cell death, was regulated by Nrf2. Unlike CinA, DNCB treatment provoked a significant reduction of intracellular GSH levels and up-regulated bcl-2 gene expression, under the control of Nrf2. This work underlies that chemical reactivity may control Nrf2-dependent gene expression leading to different cytoprotective mechanisms in DC. - Highlights: • Nrf2 controls cell death induced by contact sensitizers in dendritic cells. • DNCB reduced GSH levels and up-regulated bcl-2 gene expression unlike CinA. • Chemical reactivity controls Nrf2-dependent genes having protective effect in DC.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2017-05-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 322


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