title: Activation of selective transcription factors and cytokines by water-soluble extract from Lentinus lepideus.
abstract: We isolated a water-soluble extract, PG101, from cultured mycelia of Lentinus lepideus. Treatment of human peripheral blood mononuclear cells (PBMCs) with PG101 increased levels of TNF-alpha, IL-1beta, IL-10, and IL-12 by 100- to 1000-fold, whereas GM-CSF and IL-18 were activated by an order of magnitude. On the contrary, IFN-gamma and IL-4 were not affected. The response to PG101 occurred in a dose- and time-dependent manner. From the human PBMCs treated with PG101, TNF-alpha was a first cytokine to be activated, detectable at 2 hr post-treatment followed by IL-1beta at 6 hr post-treatment. IL-12 and IL-10 were the next to follow. GM-CSF and IL-18 both showed significant increases 24 hr after treatment. When PBMCs were sorted into various cell types, monocyte/macrophages, but not T and B cells, were the major target cell type responsive to PG101. Consistent with this result, the profile of cytokine expression upon PG101 treatment was comparable between PBMCs and a human promonocytic cell line (U937), whereas cell lines of T cell and myeloid origins did not respond to PG101. Data from a transient transfection assay involving specific reporter plasmids indicated that cellular transcription factor such as NF-kappaB, but not AP-1, was highly activated by PG101. Results from a gel retardation assay and the experiment involving a specific NF-kappaB inhibitor confirmed the involvement of NF-kappaB. Despite its significant biological effect on various cytokines, PG101 remained nontoxic in both rats and PBMCs even at a biological concentration approximately 20 times greater. PG101 demonstrates great potential as a therapeutic immune modulator.
authors.affiliation: PanGenomics Co Ltd, Biotechnology Incubating Center, Seoul 151-742, Korea.
authors.forename: Mirim
authors.initials: M
authors.lastname: Jin
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Jung
authors.forename: Jeong June
authors.initials: JJ
authors.lastname: Choi
authors.forename: Hyang
authors.initials: H
authors.lastname: Jeon
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Bongcheol
authors.initials: B
authors.lastname: Kim
authors.forename: Sung Seup
authors.initials: SS
authors.lastname: Shin
authors.forename: Jong Kyu
authors.initials: JK
authors.lastname: Lee
authors.forename: Keejung
authors.initials: K
authors.lastname: Yoon
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D020074:Lentinula / Q000737:chemistry*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology* / Q000633:toxicity; D010957:Plasmids / Q000235:genetics; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D012995:Solubility; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D011392:Proline