PMID- 24780928 OWN - NLM STAT- MEDLINE DCOM- 20150217 LR - 20211021 IS - 1523-1747 (Electronic) IS - 0022-202X (Linking) VI - 134 IP - 11 DP - 2014 Nov TI - Role of ROS and HMGB1 in contact allergen-induced IL-18 production in human keratinocytes. PG - 2719-2727 LID - S0022-202X(15)36529-5 [pii] LID - 10.1038/jid.2014.203 [doi] AB - Keratinocytes have a key role in all phases of allergic contact dermatitis. We have recently identified the possibility to use IL-18 production for the in vitro identification of contact allergens. The purpose of this study was to characterize the molecular mechanisms underlying allergen-induced IL-18 production, in order to identify the cellular source of reactive oxygen species (ROS) and the danger signals involved. The NCTC2544 cell line was exposed to three contact allergens, namely p-phenylenediamine (PPD), 2,4-dinitrochlorobenzene (DNCB), and citral, in the presence or absence of diphenylene iodonium (DPI), allopurinol, and rotenone to identify the source of ROS, and to anti-Toll-like receptor 4 antibody and glycirrizic acid to characterize the danger-associated molecular pattern molecules. In the case of PPD, the induction of IL-18 can be modulated by rotenone, allopurinol, and DPI. In the case of DNCB, rotenone completely prevents the induction of IL-18, whereas for citral, DPI completely prevents the induction of IL-18. We demonstrated the ability of all allergens tested to induce the release of high-mobility group protein B1 (HMGB1). Its sequester by glycirrizic acid significantly modulates PPD-induced IL-18 production and completely prevents DNCB- and citral-induced IL-18. We found that different intracellular sources of ROS are triggered by contact allergens, and an important role for HMGB1 in chemical allergen-induced IL-18 production was demonstrated. FAU - Galbiati, Valentina AU - Galbiati V AD - Laboratory of Toxicology, DiSFeB, Universita degli Studi di Milano, Milan, Italy. Electronic address: valentina.galbiati@unimi.it. FAU - Papale, Angela AU - Papale A AD - Laboratory of Toxicology, DiSFeB, Universita degli Studi di Milano, Milan, Italy. FAU - Galli, Corrado L AU - Galli CL AD - Laboratory of Toxicology, DiSFeB, Universita degli Studi di Milano, Milan, Italy. FAU - Marinovich, Marina AU - Marinovich M AD - Laboratory of Toxicology, DiSFeB, Universita degli Studi di Milano, Milan, Italy. FAU - Corsini, Emanuela AU - Corsini E AD - Laboratory of Toxicology, DiSFeB, Universita degli Studi di Milano, Milan, Italy. LA - eng PT - Journal Article DEP - 20140429 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Acyclic Monoterpenes) RN - 0 (Allergens) RN - 0 (Cytokines) RN - 0 (Dinitrochlorobenzene) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, human) RN - 0 (Interleukin-18) RN - 0 (Monoterpenes) RN - 0 (Onium Compounds) RN - 0 (Phenylenediamines) RN - 0 (Reactive Oxygen Species) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 6FO62043WK (Glycyrrhizic Acid) RN - 6HJ411TU98 (diphenyleneiodonium) RN - EC 3.4.22.36 (Caspase 1) RN - T7EU0O9VPP (citral) RN - U770QIT64J (4-phenylenediamine) SB - IM MH - Acyclic Monoterpenes MH - Allergens/*chemistry MH - Caspase 1/metabolism MH - Cell Line MH - Cell Survival MH - Cytokines/metabolism MH - Dermatitis, Allergic Contact/metabolism MH - Dinitrochlorobenzene/chemistry MH - Epidermis/metabolism MH - Glycyrrhizic Acid/chemistry MH - HMGB1 Protein/*metabolism MH - Humans MH - Inflammation/metabolism MH - Interleukin-18/*metabolism MH - Keratinocytes/*metabolism MH - Monoterpenes/chemistry MH - Onium Compounds/chemistry MH - Phenylenediamines/chemistry MH - Reactive Oxygen Species/*metabolism MH - Toll-Like Receptor 4/metabolism EDAT- 2014/05/02 06:00 MHDA- 2015/02/18 06:00 CRDT- 2014/05/01 06:00 PHST- 2013/09/12 00:00 [received] PHST- 2014/03/18 00:00 [revised] PHST- 2014/04/07 00:00 [accepted] PHST- 2014/05/01 06:00 [entrez] PHST- 2014/05/02 06:00 [pubmed] PHST- 2015/02/18 06:00 [medline] AID - S0022-202X(15)36529-5 [pii] AID - 10.1038/jid.2014.203 [doi] PST - ppublish SO - J Invest Dermatol. 2014 Nov;134(11):2719-2727. doi: 10.1038/jid.2014.203. Epub 2014 Apr 29.