miR-29b and miR-29c Are Involved in Toll-Like Receptor Control of Glucocorticoid-Induced Apoptosis in Human Plasmacytoid Dendritic CellsReportar como inadecuado




miR-29b and miR-29c Are Involved in Toll-Like Receptor Control of Glucocorticoid-Induced Apoptosis in Human Plasmacytoid Dendritic Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Glucocorticoids GCs are frequently used to treat many of the acute disease manifestations associated with inflammatory and autoimmune disorders. However, Toll-like receptor TLR pathway-activated plasmacytoid dendritic cells pDCs are resistant to GC-induced apoptosis, which leads to the inefficiency of GCs in the treatment of type I interferon-related autoimmune diseases, such as systemic lupus erythematosus SLE. Therefore, compounds promoting pDC apoptosis may be helpful for improving the efficacy of GCs. In this study, we performed screening to identify microRNAs miRNAs involved in TLR-inhibited GC-induced pDC apoptosis and found an array of miRNAs that may regulate pDC apoptosis. Among those demonstrating altered expression, 6 miRNAs were inhibited in TLR-activated pDCs. Bioinformatics analysis and functional studies indicated that miR-29b and miR-29c were 2 key miRNAs involved in TLR-inhibited GC-induced pDC apoptosis. Furthermore, both of these miRNAs promoted pDC apoptosis by directly targeting Mcl-1 and Bcl-2 in human primary pDCs. Our findings provide new targets that could improve the efficacy of GCs for the treatment of SLE.



Autor: Yongfeng Hong , Jianxian Wu , Jingpu Zhao, Huiping Wang, Yi Liu, Tianping Chen, Xiuli Kan, Qianshan Tao, Xianshan Shen, Kaili Yan

Fuente: http://plos.srce.hr/



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