title: Dendritic cells' death induced by contact sensitizers is controlled by Nrf2 and depends on glutathione levels.
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.
authors.affiliation: UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
authors.forename: Zeina
authors.initials: Z
authors.lastname: El Ali
authors.affiliation: IFR141 IPSIT, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Deloménie
authors.affiliation: INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Team.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Botton
authors.affiliation: UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France. Electronic address: saadia.kerdine-romer@u-psud.fr.
authors.forename: Saadia
authors.initials: S
authors.lastname: Kerdine-Römer
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D004137:Dinitrochlorobenzene / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D006241:Haptens / Q000633:toxicity*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000502:physiology*
chemical_list: D004137:Dinitrochlorobenzene; D006241:Haptens; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D000171:Acrolein; D005978:Glutathione; C012843:cinnamaldehyde
keywords: Allergy; Apoptosis; Contact sensitizers; Dendritic cells; GSH,; Nrf2; Reactive species; bcl-2; ho-1