title: miR-29b and miR-29c are involved in Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid dendritic cells.
abstract: 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.
authors.affiliation: Department of Rehabilitation, The Second Affiliated Hospital to Anhui Medical University, Economic Development Zone, Hefei City, Anhui, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Hong
authors.forename: Jianxian
authors.initials: J
authors.lastname: Wu
authors.forename: Jingpu
authors.initials: J
authors.lastname: Zhao
authors.forename: Huiping
authors.initials: H
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Tianping
authors.initials: T
authors.lastname: Chen
authors.forename: Xiuli
authors.initials: X
authors.lastname: Kan
authors.forename: Qianshan
authors.initials: Q
authors.lastname: Tao
authors.forename: Xianshan
authors.initials: X
authors.lastname: Shen
authors.forename: Kaili
authors.initials: K
authors.lastname: Yan
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhai
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019295:Computational Biology; D018899:CpG Islands; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; C579095:MCL1 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051193:Toll-Like Receptors; D003907:Dexamethasone
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