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Biological evaluation of subglutinol a as a novel immunosuppressive agent for inflammation intervention

Regina Lin1, Hyoungsu Kim2, Jiyong Hong3

  • 1Department of Immunology, Duke University Medical Center , Durham, North Carolina 27710, United States.

ACS Medicinal Chemistry Letters
|June 6, 2014
PubMed

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.

Keywords:
SubglutinolT cell activationimmunosuppressive agentinflammatory diseasemitochondrial dysfunction

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