| First Author | Wang X | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 11 | Pages | 2737-2746 |
| PubMed ID | 24933319 | Mgi Jnum | J:215932 |
| Mgi Id | MGI:5607367 | Doi | 10.1038/jid.2014.252 |
| Citation | Wang X, et al. (2014) Trichomide A, a natural cyclodepsipeptide, exerts immunosuppressive activity against activated T lymphocytes by upregulating SHP2 activation to overcome contact dermatitis. J Invest Dermatol 134(11):2737-46 |
| abstractText | Increasing numbers of people are suffering from allergic contact dermatitis. However, the immunosuppressive drug candidate with negligible toxicity is still deficient. In the present study, we identified a natural cyclodepsipeptide named trichomide A that effectively inhibited the proliferation of activated T cells and reduced the production of proinflammatory cytokines but had almost no toxic effect on naive T cells at 0.3-3 muM. In addition, trichomide A caused G0/G1 phase arrest, suppressed the activation of AKT and STAT3, and increased the level of phosphorylated SHP2 in activated T cells in dose- and time-dependent manners. Furthermore, an in vivo experiment demonstrated that trichomide A significantly ameliorated picryl chloride (PCI)-induced contact hypersensitivity in mice. Such effects of trichomide A in the aforementioned experiments were significantly reversed by the inhibition of SHP2 activity using the SHP2-specific inhibitor PHPS1 or conditional SHP2 knockout mice in T cells, suggesting the SHP2-dependent action of trichomide A. Taken together, trichomide A showed an immunosuppressive activity against T cell-mediated immune responses both in vitro and in vivo, which has potential for the treatment of immune-related skin diseases. |
