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

Abstract

Natural compounds possessing naphthopyran moiety have been attracted by their anti-bacterial, anti-fungal, 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 IFNgamma 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 IFNgamma 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.

• Authors: Jeong-Ho Hong, Eun Sun Yu, Ah-Reum Han, Joo-Won Nam, Eun-Kyoung Seo, Eun Sook Hwang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 371 Issue 2 Pg. 278-82 (Jun 27 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18435915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD4 Antigens
• Cytokines
• Furans
• Immunologic Factors
• Interleukin-2
• Naphthols
• Naphthoquinones
• Pyrans
• Pyrones
• Receptors, Antigen, T-Cell
• T-Box Domain Proteins
• T-box transcription factor TBX21
• eleutherinol
• Interferon-gamma
• eleutherin
• isoeleutherin

Topics

• Animals
• CD4 Antigens (analysis)
• Cytokines (genetics, metabolism)
• Furans (chemistry, pharmacology)
• Humans
• Immunologic Factors (chemistry, pharmacology)
• Interferon-gamma (antagonists & inhibitors, genetics, metabolism)
• Interleukin-2 (antagonists & inhibitors, genetics, metabolism)
• Lymphocyte Activation (drug effects)
• Mice
• Naphthols (chemistry, pharmacology)
• Naphthoquinones (chemistry, pharmacology)
• Pyrans (chemistry, pharmacology)
• Pyrones (chemistry, pharmacology)
• Receptors, Antigen, T-Cell (metabolism)
• T-Box Domain Proteins (metabolism)
• T-Lymphocytes, Helper-Inducer (drug effects, immunology)
• Transcription, Genetic (drug effects)