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RESEARCH PRODUCT

Effects of plant alkylphenols on cytokine production, tyrosine nitration and inflammatory damage in the efferent phase of contact hypersensitivity

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Background and purpose: The phenolic compounds isoprenylhydroquinone glucoside (IHG), 3,5-dicaffeoylquinic acid (DCA), and its methyl ester (DCE) have previously been shown to inhibit both contact hypersensitivity (CHS) and peroxynitrite reactivity. The present work seeks to establish a relationship between the anti-inflammatory effect and the release of cytokines and tyrosine nitration in skin. Experimental approach: Murine CHS was developed by means of sensitization and challenge with dinitrofluorobenzene (DNFB) or oxazolone. Ear swelling was measured 24 and 96 h after challenge. Interleukin (IL)-1b, IL-4, and tumour necrosis factor (TNF)-a were measured by ELISA; and the expression of inducible nitric oxide synthase (iNOS) was detected by Western blotting. Histological samples were analysed for 3-nitrotyrosine. Key results: In the oxazolone model, DCE reduced the 24 h swelling by 54% whereas the effect of DCA was lower (40% inhibition). All the test compounds reduced IL-1b values 24 h after challenge with DNFB or oxazolone, DCE particularly inhibited IL-4 production (74% and 78%, respectively; Po0.01). Tyrosine nitration was also markedly reduced by DCE. In general, the test compounds limited the presence of polymorphonuclear (PMN) leukocytes in the skin. Conclusions and implications: These results suggest that the effect of 3,5-dicaffeoylquinic esters on CHS is associated with a decrease in the production of interleukins, but not with the inhibition of iNOS expression. Moreover, esterification of the carboxyl group at C-1 enhanced protection against tyrosine nitration in the skin. British Journal of Pharmacology (2007) 152, 366–373; doi:10.1038/sj.bjp.0707402; published online 30 July 2007