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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 435916, 14 pages
http://dx.doi.org/10.1155/2013/435916
Research Article

4-Hydroxy-17-methylincisterol from Agaricus blazei Decreased Cytokine Production and Cell Proliferation in Human Peripheral Blood Mononuclear Cells via Inhibition of NF-AT and NF-B Activation

1National Research Institute of Chinese Medicine, No. 155-1, Section 2, Li-Nung Street, Shih-Pai 112, Taipei, Taiwan
2LS212, Laboratory of Molecular Pharmacology, Department of Life Science, Fu-Jen Catholic University, No. 510, Chung-Cheng Road, Hsinchuang 242, New Taipei, Taiwan
3Graduate School of Biotechnology, Hungkuang University, No. 34, Chung-Chie Road, Sha Lu 443, Taichung, Taiwan
4Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, No. 155, Section 2, Li-Nung Street, Shih-Pai 112, Taipei, Taiwan

Received 26 September 2012; Revised 10 December 2012; Accepted 10 December 2012

Academic Editor: Juliano Ferreira

Copyright © 2013 Wei-Jern Tsai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Agaricus blazei Murill is an edible and medicinal mushroom. In the previous study, we have proved that extracts of A. blazei inhibit human peripheral blood mononuclear cell (PBMC) proliferation activated with phytohemagglutinin (PHA). Currently, we purified 4-hydroxy-17-methylincisterol (4-HM; C21H33O3) from A. blazei investigated its regulatory effects on cytokine productions and cell proliferation of PBMC induced by PHA. The results indicated that 4-HM suppressed, in activated PBMC, the production and mRNA expression of interleukin-2 (IL-2), IL-4, tumor necrosis factor-α, and interferon-γ in a concentration-dependent manner. This inhibition was not related to cell viability. While 4-HM did not affect ERK phosphorylation and its downstream c-fos gene expression in PBMC induced by PHA, it decreased both NF-AT and NF-κB activation. The upstream signaling of NF-AT and NF-κB, intracellular calcium concentrations (), and protein kinase C theta (PKC θ) activation in PHA-treated PBMC were reduced by 4-HM. The data demonstrated that the suppressant effects of 4-HM on cell proliferation in PBMC activated by PHA appeared to be mediated, at least in part, through inhibition of Ca2+ mobilization and PKC θ activation, NF-AT and NF-κB activation, and cytokine transcripts and productions of PBMC. We suggested that A. blazei contained a potential immunomodulator 4-HM.