miR-29b and miR-29c are involved in Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid dendritic cells

• Published in: PloS one Vol. 8; no. 7; p. e69926
• Main Authors: Hong, Yongfeng, Wu, Jianxian, Zhao, Jingpu, Wang, Huiping, Liu, Yi, Chen, Tianping, Kan, Xiuli, Tao, Qianshan, Shen, Xianshan, Yan, Kaili, Zhai, Zhimin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.07.2013; Public Library of Science (PLoS)
• Subjects: Analysis; Apoptosis; Apoptosis - drug effects; Autoimmune diseases; B cells; Bcl-2 protein; Bioinformatics; Biological response modifiers; Biology; Cancer therapies; Care and treatment; Chronic conditions; Computational Biology; CpG Islands; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - metabolism; Dexamethasone - pharmacology; Disease; Drugs; Economic development; Gene expression; Genomics; Glucocorticoids; Glucocorticoids - pharmacology; Hematology; Hospitals; Humans; Immune system; Infections; Inflammatory diseases; Interferon; Leukemia; Lupus; Mcl-1 protein; Medical treatment; Medicine; MicroRNA; MicroRNAs; MicroRNAs - metabolism; miRNA; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Proteins; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rehabilitation; Steroids (Organic compounds); Systemic lupus erythematosus; Toll-like receptors; Toll-Like Receptors - metabolism; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069926

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.