title: Biological evaluation of subglutinol a as a novel immunosuppressive agent for inflammation intervention.
abstract: Subglutinol A (1) is an immunosuppressive natural product isolated from Fusarium subglutinans, an endophytic fungus from the vine Tripterygium wilfordii. We show that 1 exerts multimodal immune-suppressive effects on activated T cells in vitro: subglutinol A (1) effectively blocks T cell proliferation and survival while profoundly inhibiting pro-inflammatory IFNγ and IL-17 production by fully differentiated effector Th1 and Th17 cells. Our data further reveal that 1 may exert its anti-inflammatory effects by exacerbating mitochondrial damage in T cells. Additionally, we demonstrate that 1 significantly reduces lymphocytic infiltration into the footpad and ameliorates footpad swelling in the mouse model of Th1-driven delayed-type hypersensitivity. These results suggest the potential of 1 as a novel therapeutic for inflammatory diseases.
authors.affiliation: Department of Immunology, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Regina
authors.initials: R
authors.lastname: Lin
authors.affiliation: Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Hyoungsu
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Duke University , Durham, North Carolina 27708, United States ; Department of Pharmacology and Cancer Biology, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Immunology, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
keywords: Subglutinol; T cell activation; immunosuppressive agent; inflammatory disease; mitochondrial dysfunction