Contact sensitizers modulate the arachidonic acid metabolism of PMA-differentiated U-937 monocytic cells activated by LPS

Journal Article · Sat Oct 01 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.06.025· OSTI ID:21587845

Bernad, Jose; Dardenne, Christophe ^[1]; Verda, Denis; Meunier, Jean Roch; Rousset, Francoise; Martinozzi-Teissier, Silvia ^[2]; Pipy, Bernard ^[1]

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1. UMD3, INSERM-IFR150, Universite de Toulouse, Universite Paul Sabatier, 31062 Toulouse (France)
2. L'Oreal R and I, 93600 Aulnay-sous-Bois (France)

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-1{beta} and TNF-{alpha}) 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{sub 2,} TxB{sub 2} and PGD{sub 2}), eugenol and cinnamaldehyde inhibiting also the production of IL-1{beta} and TNF-{alpha}. We further demonstrated that there is no unique PGE{sub 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. - Highlights: > We investigated how contact sensitizers modulate an inflammatory response. > We used macrophage-differentiated cell line, U-937 treated with PMA/LPS. > Sensitizers specifically inhibit the production of COX metabolites (PGE2, TxB2). > Several mechanisms of inhibition: COX-2 expression/enzymatic activity, isomerases. > New insight in the biochemical properties of sensitizers.

• OSTI ID: 21587845
• Journal Information: Toxicology and Applied Pharmacology, Vol. 256, Issue 1; Other Information: DOI: 10.1016/j.taap.2011.06.025; PII: S0041-008X(11)00262-6; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARACHIDONIC ACID
INFLAMMATION
ISOMERASES
LACTIC ACID
LYMPHOKINES
METABOLISM
METABOLITES
SENSITIZERS
SKIN
BODY
CARBOXYLIC ACIDS
ENZYMES
GROWTH FACTORS
HYDROXY ACIDS
MITOGENS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PROTEINS
REAGENTS
SYMPTOMS