Background: Th17-mediated inflammatory responses are detrimental for allograft acceptance and long-term survival after transplantation. Shikonin is a naphthoquinone pigment isolated from a traditional medicinal herb Lithospermum erythrorhizon, and has been reported to have anti-inflammatory activities through ERK, AKT and NF-κB signaling pathways. Whether and how Shikonin may control inflammatory responses by interfering Th17 development pathway has not been defined. In this study, we examined the effects of Shikonin on IL-6 signals and Th17 development.

Methods: Human HEPG2 cells were treated with IL-6 (20ng/ml) or IFNγ (20ng/ml), with or without Shikonin (25mM), then phosphorylated and total STAT3 and STAT1 were measured by western blotting. For Th17 differentiation, naïve CD4⁺ T cells isolated from wild type C57BL/6 mice were stimulated by anti-CD3 and anti-CD28 along with IL-6 (20ng/ml) plus TGFβ (10ng/ml) for 3 days, with or without Shikonin (25mM), and IL-17 expression was examined by quantitative real-time RT-PCR.

Results: Shikonin selectively inhibited STAT3 but not STAT1 activation in human HEPG2 cells. Under conditions of Th17 differentiation, Shikonin completely impaired IL-6 plus TGFβ driven IL-17 expression and Th17 development.

Conclusion: Our results identify a novel mechanism of Shikonin inhibiting Th17 development through selectively repressing STAT3 activation, and reveal a potential therapeutic property of Shikonin to suppress Th17-mediated inflammatory responses and benefit allograft survival.

CITATION INFORMATION: Fang H., Zhang R., Liang F., Chen Q., Ochando J., Ding Y., Xu J. Shikonin Inhibits Th17 Development through Repressing STAT3 Activation Am J Transplant. 2017;17 (suppl 3).

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