Obaculactone exerts a novel ameliorating effect on contact dermatitis through regulating T lymphocyte

It is still deficient that an immunosuppressant with a negligible toxicity for patients suffering from contact hypersensitivity. In the present study, we identified a natural occurring compound named obaculactone that effectively alleviated the macroscopic and microscopic appearances of the contact hypersensitivity, while it scarcely possessed toxic effect on mice at 5-20mg/kg. The mRNAs of IL-2, IL-17a, TNF-α and IFN-γ expressed in lymph nodes of mice with dermatitis were also decreased by obaculactone in a dose-dependent manner. Moreover, the hypersensitivity couldn't be adoptively transferred from obaculactone-treated donor mice to normal mice. In vitro study, proliferation arrest in activated hapten-specific T cells and anti-CD3/CD28 stimulated T cells were observed in obaculactone-treated groups. In addition, the enhanced expressions of CD25 and CD69 in activated T cells were reduced by obaculactone. Meanwhile, obaculactone caused G0/G1 phase arrest and up-regulated the levels of cleaved-caspases and cleaved-PARP inducing apoptosis in activated T cells. Taken together, suppressing cell growth in activated T lymphocytes may contribute to the novel ameliorating effect for obaculactone against the contact hypersensitivity.