title: Epigallocatechin gallate modulates cytokine production by bone marrow-derived dendritic cells stimulated with lipopolysaccharide or muramyldipeptide, or infected with Legionella pneumophila.
abstract: The primary polyphenol in green tea extract is the catechin epigallocatechin gallate (EGCG). Various studies have shown significant suppressive effects of catechin on mammalian cells, either tumor or normal cells, including lymphoid cells. Previous studies from this laboratory reported that EGCG has marked suppressive activity on murine macrophages infected with the intracellular bacterium Legionella pneumophila (Lp), an effect mediated by enhanced production of both tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (IFN-gamma). In the present study, primary murine bone marrow (BM)-derived dendritic cells (DCs), a phagocytic monocytic cell essential for innate immunity to intracellular microorganisms, such as Lp, were stimulated in vitro with the microbial stimulant lipopolysaccharide (LPS) from gram-negative bacteria, the cell wall component from gram-positive bacteria muramyldipeptide (MDP) or infected with Lp. Production of the T helper cell (Th1)-activating cytokine, interleukin-12 (IL-12) and the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha),produced mainly by phagocytic cells and important for antimicrobial immunity, was determined in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Treatment of the cells with EGCG inhibited, in a dose-dependent manner, production of IL-12. In contrast, enhanced production of TNF-alpha occurred in a dose-dependent manner in the DC cultures stimulated with either soluble bacterial product or infected with Lp. Thus, the results of this study show that the EGCG catechin has a marked effect in modulating production of these immunoregulatory cytokines in stimulated DCs, which are important for antimicrobial immunity, especially innate immunity. Further studies are necessary to characterize the physiologic function of the effect of EGCG on TNF-alpha and IL-12 during Lp infection, and the mechanisms involved.
authors.affiliation: Department of Medical Microbiology and Immunology, University of South Florida, Tampa, FL 33612, USA.
authors.forename: James
authors.initials: J
authors.lastname: Rogers
authors.forename: Izabella
authors.initials: I
authors.lastname: Perkins
authors.forename: Alberto
authors.initials: A
authors.lastname: van Olphen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Burdash
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Klein
authors.forename: Herman
authors.initials: H
authors.lastname: Friedman
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007113:Immunity, Innate; D016952:Legionella pneumophila / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D002392:Catechin; C045651:epigallocatechin gallate