Isoeleutherin and eleutherinol, naturally occurring selective modulators of Th cell-mediated immune responses

초록

Natural compounds possessing naphthopyran moiety have been attracted by their anti-bacterial, antifungal, and anti-viral activities, as well as anti-tumor activities. Although chemical structures were critical for the potential biological activities, the detailed functional mechanisms remained unclear. Here, we have studied the effects of naphthopyran derivatives (eleutherin, isoeleutherin, and eleutherinol) on T helper cell-mediated immune responses to understand the mechanisms of their anti-microbial and anti-tumor activities. The study revealed that isoeleutherin, which has 1,4-naphthoquinone ring with alpha-methyl group, selectively and specifically stimulated IFN gamma production through the activation of T-bet gene transcription, thus enhancing Th1-mediated immune responses. However, a natural naphthopyran-4-one, eleutherinol dramatically inhibited both IFN gamma and IL-2 productions during Th cell activation by Suppressing the gene transcriptions of cytokines. Therefore, we suggest that the chemical modification and chirality of naphthopyran moiety in isoeleutherin and eleutherinol may be critical for the selective modulation of T helper cell-mediated immune responses. (C) 2008 Elsevier Inc. All rights reserved.

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