RRC ID 21802
Author El Ali Z, Gerbeix C, Hemon P, Esser PR, Martin SF, Pallardy M, Kerdine-Römer S.
Title Allergic skin inflammation induced by chemical sensitizers is controlled by the transcription factor Nrf2.
Journal Toxicol Sci
Abstract Allergic contact dermatitis (ACD) is induced by low-molecular weight electrophilic chemicals and metal ions. Chemical contact sensitizers trigger reactive oxygen species production and provoke electrophilic stress, leading to the accumulation of the transcription factor nuclear-related factor 2 (Nrf2) in innate immune cell types. The objective of this work was to identify the role of Nrf2 in the regulation of ACD. We used the local lymph node assay (LLNA) and the mouse ear swelling test (MEST) to study the role of Nrf2 in both the sensitization and elicitation phase in nrf2 knockout (nrf2(-/-)) and wild-type (nrf2(+/+)) mice. Five chemicals were used: two compounds known to react with cysteine residues, 2,4-dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA); one sensitizer known to exhibit mixed reactivity to cysteine and lysine residues, isophorone diisocyanate; and one reacting specifically with lysine residues, trimellitic anhydride and croton oil, a well-known irritant. In the MEST assay, DNCB (1 and 2%) induced a significant increase in ear thickness in nrf2(-/-) compared with nrf2(+/+) mice, suggesting a role for Nrf2 in the control of the inflammatory process. When DNCB was used at 0.25 and 0.5% or when mice were treated with CinA, inflammation was found only in nrf2(-/-) mice. In the LLNA, all chemical sensitizers induced an increase of lymphocyte proliferation in nrf2(-/-) compared with nrf2(+/+) mice for the same chemical concentration. These results reveal an important role for Nrf2 in controlling ACD and lymphocyte proliferation in response to sensitizers.
Volume 134(1)
Pages 39-48
Published 2013-7-1
DOI 10.1093/toxsci/kft084
PII kft084
PMID 23564646
MeSH Animals Dermatitis, Allergic Contact / etiology Dermatitis, Allergic Contact / immunology Dermatitis, Allergic Contact / metabolism* Dermatitis, Allergic Contact / pathology Dose-Response Relationship, Drug Irritants / chemistry* Irritants / toxicity* Local Lymph Node Assay Mice Mice, Inbred C57BL Mice, Knockout NF-E2-Related Factor 2 / genetics NF-E2-Related Factor 2 / immunology NF-E2-Related Factor 2 / metabolism* Skin / drug effects* Skin / immunology Skin / metabolism Skin / pathology Structure-Activity Relationship
IF 3.703
Times Cited 46
Mice RBRC01390