Immune-suppressive activity of punicalagin via inhibition of NFAT activation

Since T cell activation is central to the development of autoimmune diseases, we screened a natural product library comprising 1400 samples of medicinal herbal extracts, to identify compounds that suppress T cell activity. Punicalagin (PCG) isolated from the fruit of Punica granatum was identified a...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-07, Vol.371 (4), p.799-803
Main Authors: Lee, Sang-Ik, Kim, Byoung-Soo, Kim, Kyoung-Shin, Lee, Samkeun, Shin, Kwang-Soo, Lim, Jong-Soon
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ACETATES
Animals
AUDITORY ORGANS
CD4-Positive T-Lymphocytes - drug effects
CD4-Positive T-Lymphocytes - immunology
DISEASES
Ear
EDEMA
Edema - chemically induced
Edema - immunology
FRUITS
Humans
Hydrolyzable Tannins - isolation & purification
Hydrolyzable Tannins - pharmacology
Immune suppressant
Immunosuppressive Agents - pharmacology
IN VIVO
INHIBITION
Interleukin-2
Interleukin-2 - genetics
Interleukin-2 - metabolism
Jurkat Cells
LEUKOCYTES
Lymphocyte Activation - drug effects
Lymphocyte Culture Test, Mixed
MICE
Mice, Inbred Strains
Mixed leukocytes reaction
Natural product library
NFATC Transcription Factors - antagonists & inhibitors
Nuclear factor of activated T cells
PATHOLOGY
PMA-induced ear edema
PROTEINS
Punica granatum
Punicaceae - chemistry
Punicalagin
Tetradecanoylphorbol Acetate - toxicity
TOXICITY
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Summary:Since T cell activation is central to the development of autoimmune diseases, we screened a natural product library comprising 1400 samples of medicinal herbal extracts, to identify compounds that suppress T cell activity. Punicalagin (PCG) isolated from the fruit of Punica granatum was identified as a potent immune suppressant, based on its inhibitory action on the activation of the nuclear factor of activated T cells (NFAT). PCG downregulated the mRNA and soluble protein expression of interleukin-2 from anti-CD3/anti-CD28-stimulated murine splenic CD4+ T cells and suppressed mixed leukocytes reaction (MLR) without exhibiting cytotoxicity to the cells. In vivo, the PCG treatment inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice and decreased CD3+ T cell infiltration of the inflamed tissue. These results suggest that PCG could be a potential candidate for the therapeutics of various immune pathologies.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.04.150