TNF-α-mediated microRNA-136 induces differentiation of myeloid cells by targeting NFIA.
Immune cell-lineage specification and function are influenced by progenitor origin and environmental factors. The mechanism of differentiation of immune cells, such as neutrophils, monocytes, and myeloid-derived suppressor cells, in inflammatory environments has not been elucidated completely. In this study, we have identified human microRNA-136 as a positive regulator of the differentiation of granulocytes and monocytes. Ectopic microRNA-136 induced cells to express higher levels of CD11b, CD14, and C/EBPε, secrete more cytokines, and synthesize higher levels of reactive oxygen species and H(2)O(2). microRNA-136 was shown to target and degrade multiple differentiation-associated molecules, such as the transcription factor NFIA, which induced the release of another microRNA, microRNA-223, with the ability to promote CD11b expression. Furthermore, microRNA-136 expression was remarkably increased by TNF-α, which activated NF-κB to bind to the DNA-promoter region controlling microRNA-136 expression. Additionally, TNF-α may alter NFIA expression through its modulation of microRNA-136 expression. Thus, TNF-α-mediated microRNA-136 may play a critical role in the generation and differentiation of inflammatory immune cells.
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
Shiyue
S
Mei
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
Yu
Y
Liu
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
Xue
X
Wu
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
Qingsheng
Q
He
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
Siping
S
Min
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
Ling
L
Li
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China.
Yuan
Y
Zhang
*Department of Immunology, School of Medicine, State Key Laboratory of Medicinal Chemical Biology, and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, P. R. China ryang@nankai.edu.cn.
Rongcun
R
Yang
D020413:3' Untranslated Regions / Q000235:genetics; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D022423:Myeloid Cells / Q000166:cytology* / Q000187:drug effects; D038042:Myelopoiesis / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D051839:NFI Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009841:Oligonucleotides / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D020413:3' Untranslated Regions; D039481:CD11b Antigen; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; C577037:MIRN136 microRNA, human; C000608124:MIRN233 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D051839:NFI Transcription Factors; C497592:NFIA protein, human; D009841:Oligonucleotides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide
hematopoietic; inflammatory environment; neutrophil