PMID- 23564646
OWN - NLM
STAT- MEDLINE
DCOM- 20140128
LR  - 20130627
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 134
IP  - 1
DP  - 2013 Jul
TI  - Allergic skin inflammation induced by chemical sensitizers is controlled by the 
      transcription factor Nrf2.
PG  - 39-48
LID - 10.1093/toxsci/kft084 [doi]
AB  - 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.
FAU - El Ali, Zeina
AU  - El Ali Z
AD  - UnivSud, INSERM UMR-996, Faculty of Pharmacy, Chatenay-Malabry, France.
FAU - Gerbeix, Cedric
AU  - Gerbeix C
FAU - Hemon, Patrice
AU  - Hemon P
FAU - Esser, Philipp R
AU  - Esser PR
FAU - Martin, Stefan F
AU  - Martin SF
FAU - Pallardy, Marc
AU  - Pallardy M
FAU - Kerdine-Romer, Saadia
AU  - Kerdine-Romer S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130405
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Irritants)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Dermatitis, Allergic Contact/etiology/immunology/*metabolism/pathology
MH  - Dose-Response Relationship, Drug
MH  - Irritants/*chemistry/*toxicity
MH  - Local Lymph Node Assay
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-E2-Related Factor 2/genetics/immunology/*metabolism
MH  - Skin/*drug effects/immunology/metabolism/pathology
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Nrf2
OT  - chemicals sensitizers
OT  - contact hypersensitivity
OT  - haptens
OT  - irritation
EDAT- 2013/04/09 06:00
MHDA- 2014/01/29 06:00
CRDT- 2013/04/09 06:00
PHST- 2013/04/09 06:00 [entrez]
PHST- 2013/04/09 06:00 [pubmed]
PHST- 2014/01/29 06:00 [medline]
AID - kft084 [pii]
AID - 10.1093/toxsci/kft084 [doi]
PST - ppublish
SO  - Toxicol Sci. 2013 Jul;134(1):39-48. doi: 10.1093/toxsci/kft084. Epub 2013 Apr 5.