| First Author | Meng X | Year | 2013 |
| Journal | J Leukoc Biol | Volume | 93 |
| Issue | 1 | Pages | 83-93 |
| PubMed ID | 23142729 | Mgi Jnum | J:193745 |
| Mgi Id | MGI:5469514 | Doi | 10.1189/jlb.0812402 |
| Citation | Meng X, et al. (2013) A novel tylophorine analog W-8 up-regulates forkhead boxP3 expression and ameliorates murine colitis. J Leukoc Biol 93(1):83-93 |
| abstractText | Tylophorine and analogs are phenanthroindolizidine alkaloids, several of which have been reported to have anticancer, antiviral, and anti-inflammatory properties. However, their function in the immune system remains widely unknown. Transcription factor Foxp3 is critical for the development and function of Treg, which down-regulates the immune system and maintains tolerance to self-antigens. In the present study, we defined a novel tylophorine analog, W-8, enhanced TGF-beta-induced Foxp3 expression at the mRNA and the protein levels. Interestingly, W-8 synergistically increased the level of TGF-beta-induced p-Smad3 through inhibition of the AKT/mTOR pathway and enhanced the demethylation of the promoter region of the Foxp3 through inhibition of the ERK pathway and DNMT1 expression. Moreover, administration of W-8 suppressed TNBS-induced murine colitis and increased Tregs in lymphoid tissues. Finally, W-8 enhanced conversion of naive T cells to Tregs in vivo. In summary, our results defined a novel compound that enhanced Foxp3 expression through transcriptional and epigenetic programs, and it might serve as a therapeutic agent for inflammatory diseases. |
