title: The effect of enzymatically polymerised polyphenols on CD4 binding and cytokine production in murine splenocytes.
abstract: High-molecular weight polymerised polyphenols have been shown to exhibit anti-influenza virus, anti-HIV, and anti-cancer activities. The purpose of this study was to evaluate the immunomodulating activities of enzymatically polymerised polyphenols, and to clarify the underlying mechanisms of their effects. The cytokine-inducing activity of the enzymatically polymerised polyphenols derived from caffeic acid (CA), ferulic acid (FA), and p-coumaric acid (CoA) was investigated using murine splenocytes. Polymerised polyphenols, but not non-polymerised polyphenols, induced cytokine synthesis in murine splenocytes. Polymerised polyphenols induced several cytokines in murine splenocytes, with interferon-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most prominent. The underlying mechanisms of the effects of the polymerised polyphenols were then studied using neutralising antibodies and fluorescent-activated cell sorting (FACS) analysis. Our results show that polymerised polyphenols increased IFN-γ and GM-CSF production in splenocytes. In addition, the anti-CD4 neutralised monoclonal antibody (mAb) inhibited polymerised polyphenol-induced IFN-γ and GM-CSF secretion. Moreover, polymerised polyphenols bound directly to a recombinant CD4 protein, and FACS analysis confirmed that interaction occurs between polymerised polyphenols and CD4 molecules expressed on the cell surface. In this study, we clearly demonstrated that enzymatic polymerisation confers immunoactivating potential to phenylpropanoic acids, and CD4 plays a key role in their cytokine-inducing activity.
authors.affiliation: Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamanaka
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tamiya
authors.forename: Masuro
authors.initials: M
authors.lastname: Motoi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Noriko N
authors.initials: NN
authors.lastname: Miura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058105:Polymerization; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; D007155:Immunologic Factors; D059808:Polyphenols; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor