Health & Environmental Research Online (HERO)


Print Feedback Export to File
6957473 
Journal Article 
Abstract 
Nrf2 controls skin inflammation provoked by chemical allergens regardless of the chemical reactivity of contact sensitizers 
El Ali, Z; Gerbeix, C; Pearson, N; Forster, R; Pallardy, M; Kerdine-Roemer, S 
2015 
1 
Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 
238 
2 
S220-S220 
English 
WOS:000370693801483 
Chemical sensitizers inducing contact hypersensitivity (CHS) are known to induce reactive oxygen species (ROS). The Nrf2/Keap1 pathway is central for detoxification. Nrf2 plays a central role in protecting cells from ROS and other electrophiles. Recently, we have demonstrated that allergic skin inflammation induced by chemical sensitizers was controlled by Nrf2. In order to study the role of Nrf2 in response to chemicals that react with different amino acids, various compounds were tested using the Mouse Ear Swelling Test (MEST) and the Local Lymph Node Assay (LLNA). These studies were performed in nrf2 knock out (KO) and in wild type (WT) mice. Eleven chemicals were used: two molecules known to react with cysteine residues, trinitrochlorobenzene (TNCB) and diphenylcyclopropenone (DPC); four molecules known to exhibit mixed reactivity to cysteine and lysine residues, isophorone diisocyanate (IPDI), 4,4′ methylene diphenyl diisocyanate (4, 4′ MDI), toluene diisocyanate (TDI) and 1-phenyl-1,2-propanedione (P2P); three molecules reacting specifically with lysine residues, phthalic anhydride (PA), trimellitic anhydride (TMA) and 3,4-dihydrocoumarin (DHC); one pro-hapten, eugenol and one pro/pre-hapten p-phenylenediamine (pPD). The MEST results showed that all tested compounds induced a greater increase in the ear thickness in nrf2−/− mice (KO) than in nrf2+/+ mice (WT). Furthermore, the swelling increase was dose dependent. The non-sensitizing dose of all compounds in WT mice efficiently induced CHS in KO mice. Results obtained in the LLNA showed that lysine compounds (PA & TMA) and isocyanate compounds (IPDI & TDI) induced an increase of lymphocyte proliferation in KO and WT mice. Regardless of the chemical used, the stimulation index (SI) for a similar concentration was higher in KO mice than in WT mice. Nrf2 controls the inflammation response and the lymphocyte proliferation, involved in allergic response to chemical sensitizers having different reactivities to aminoacids.