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Anti-inflammatory activity of p-coumaryl alcohol-γ-O-methyl ether is mediated through modulation of interferon-γ production in Th cells

Title
Anti-inflammatory activity of p-coumaryl alcohol-γ-O-methyl ether is mediated through modulation of interferon-γ production in Th cells
Authors
Yu E.-S.Min H.-J.Lee K.Lee M.-S.Nam J.-W.Seo E.-K.Hong J.-H.Hwang E.-S.
Ewha Authors
이경림서은경황은숙
SCOPUS Author ID
이경림scopus; 서은경scopus; 황은숙scopus
Issue Date
2009
Journal Title
British Journal of Pharmacology
ISSN
0007-1188JCR Link
Citation
vol. 156, no. 7, pp. 1107 - 1114
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Background and purpose: p-Coumaryl alcohol-γ-O-methyl ether (CAME) was isolated from Alpinia galanga and shown to contain a phenylpropanoid structure similar to p-coumaryl diacetate (CDA). CDA is known to have antioxidant and anti-inflammatory activity, but the biochemical activities of CAME are unknown. Inflammation is mediated by inflammatory cytokine production, in particular, by CD4+ T helper cells (Th cells), but it is unclear whether phenylpropanoids affect cytokine production in Th cells. In this study, we decided to investigate the functions of CAME and CDA in CD4+ Th cells. Experimental approach: Mouse CD4+ Th cells were isolated from C57BL6 mice and stimulated with an antibody against T cell receptors in the presence of phenylpropanoids. Cytokine production was measured by elisa and intracellular cytokine staining. Gene knockout mice and tetracycline-inducible transgenic mice were used to examine the molecular mechanisms of phenylpropanoids on modulation of cytokine production. Key results: CAME potently reduced intracellular reactive oxygen species in Th cells, as does CDA. However, although CDA was cytotoxic, CAME selectively and potently suppresses interferon-γ (IFNγ) production in CD4+ Th cells, without toxicity. This effect was caused by attenuated expression of the transcription factor, T-box protein expressed in T cells (T-bet), and T-bet was essential for CAME to inhibit IFNγ production in CD4+ Th cells. Conclusions and implications: CAME selectively and substantially suppresses IFNγ production in CD4+ Th cells by decreasing T-bet expression. As increased IFNγ production by CD4+ Th cells can mediate inflammatory immune responses, a selective IFNγ suppressor, such as CAME may be an effective, naturally occurring, compound for modulating inflammatory immune disorders. © 2009 The British Pharmacological Society.
DOI
10.1111/j.1476-5381.2009.00114.x
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약학대학 > 약학과 > Journal papers
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