Role of growth hormone in maturation and activation of dendritic cells via miR-200a and the Keap1/Nrf2 pathway.
OBJECTIVE
Dendritic cells (DCs) are antigen-presenting cells that participate in the immune response; recently, it has been reported that growth hormone (GH) promotes their maturation. The aim of this study was to investigate mechanisms by which GH acts on DC maturation and activation.


METHODS
Human peripheral blood monocytes (HPBMs) were induced to become immature DCs and treated with GH to obtain mature DCs. An osteosarcoma mouse model was established by injection of LM8 cells to investigate anti-tumour effect of GH-induced DCs in vivo.


RESULTS
After administration of GH, DCs reduced miR-200a expression and nuclear Nrf2 accumulation; miR-200a down-regulation inhibited DC maturation. Nrf2 ubiquitination level was increased by Keap1 overexpression in murine bone marrow derived dendritic cells (BMDCs), which was cancelled by miR-200a in GH exposed cells. In vivo, tumour volume was significantly reduced by GH-treated DCs and the effect was reversed by overexpression of miR-200a.


CONCLUSIONS
GH promoted maturation and activation of DCs, and regulation of miR-200a played a part in this process by modulation of the Keap1/Nrf2 pathway.
Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Qiu-Liang
QL
Liu
Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Jiao
J
Zhang
Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Xin
X
Liu
Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Jing-Yao
JY
Gao
D020413:3' Untranslated Regions; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D018215:Osteoblastoma / Q000473:pathology / Q000628:therapy; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014183:Transplantation, Heterologous; D054875:Ubiquitination / Q000187:drug effects
D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D013006:Growth Hormone