title: Contact sensitizers modulate the arachidonic acid metabolism of PMA-differentiated U-937 monocytic cells activated by LPS.
abstract: For the effective induction of a hapten-specific T cell immune response toward contact sensitizers, in addition to covalent-modification of skin proteins, the redox and inflammatory statuses of activated dendritic cells are crucial. The aim of this study was to better understand how sensitizers modulate an inflammatory response through cytokines production and COX metabolism cascade. To address this purpose, we used the human monocytic-like U-937 cell line differentiated by phorbol myristate acetate (PMA) and investigated the effect of 6 contact sensitizers (DNCB, PPD, hydroquinone, propyl gallate, cinnamaldehyde and eugenol) and 3 non sensitizers (lactic acid, glycerol and tween 20) on the production of pro-inflammatory cytokines (IL-1β and TNF-α) and on the arachidonic acid metabolic profile after bacterial lipopolysaccharide (LPS) stimulation. Our results showed that among the tested molecules, all sensitizers specifically prevent the production of PMA/LPS-induced COX-2 metabolites (PGE(2,) TxB(2) and PGD(2)), eugenol and cinnamaldehyde inhibiting also the production of IL-1β and TNF-α. We further demonstrated that there is no unique PGE(2) inhibition mechanism: while the release of arachidonic acid (AA) from membrane phospholipids does not appear do be a target of modulation, COX-2 expression and/or COX-2 enzymatic activity are the major steps of prostaglandin synthesis that are inhibited by sensitizers. Altogether these results add a new insight into the multiple biochemical effects described for sensitizers.
authors.affiliation: L'Oréal R&I, 93600 Aulnay-sous-Bois, France. adelbufalo@rd.loreal.com
authors.forename: Aurélia
authors.initials: A
authors.lastname: Del Bufalo
authors.forename: José
authors.initials: J
authors.lastname: Bernad
authors.forename: Christophe
authors.initials: C
authors.lastname: Dardenne
authors.forename: Denis
authors.initials: D
authors.lastname: Verda
authors.forename: Jean Roch
authors.initials: JR
authors.lastname: Meunier
authors.forename: Françoise
authors.initials: F
authors.lastname: Rousset
authors.forename: Silvia
authors.initials: S
authors.lastname: Martinozzi-Teissier
authors.forename: Bernard
authors.initials: B
authors.lastname: Pipy
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology*; D006241:Haptens / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity*; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D020298:U937 Cells
chemical_list: D006241:Haptens; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016718:Arachidonic Acid; D013755:Tetradecanoylphorbol Acetate