PMID- 25290620 OWN - NLM STAT- MEDLINE DCOM- 20150217 LR - 20201222 IS - 1090-2163 (Electronic) IS - 0008-8749 (Linking) VI - 292 IP - 1-2 DP - 2014 Nov-Dec TI - Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203. PG - 65-9 LID - S0008-8749(14)00147-6 [pii] LID - 10.1016/j.cellimm.2014.09.004 [doi] AB - MicroRNAs (miRNAs) are aberrant in many human tumors which can be transferred to immune cells by tumor-derived exosomes. Dendritic cells (DCs) play an important role in activation of immune response. However, the effect of tumor-derived exosomes on toll-like receptor (TLR) in DCs remains unclear. We investigated the influence of pancreatic cancer derived exosomes on TLR4, and downstream cytokines via miR-203. Our results showed that miR-203 expressed in panc-1 cells and exosomes, and upregulated in exosomes-treated DCs. TLR4 decreased after treatment of exosomes and miR-203 mimics, while increased in exosomes-treated DCs by miR-203 inhibitors. But the mRNA level of TLR4 was not significantly different between DCs and exosomes-treated DCs. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-12 (IL-12) also decreased under treatment of exosomes and miR-203 mimics, both of which increased in exosomes-treated DCs by miR-203 inhibitors. Collectively, pancreatic cancer derived exosomes downregulate TLR4 and downstream cytokines in DCs via miR-203. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Zhou, Min AU - Zhou M AD - Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. FAU - Chen, Jionghuang AU - Chen J AD - Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. FAU - Zhou, Liangjing AU - Zhou L AD - Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. FAU - Chen, Wenchao AU - Chen W AD - Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. FAU - Ding, Guoping AU - Ding G AD - Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. FAU - Cao, Liping AU - Cao L AD - Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. Electronic address: zjulipingcao@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140928 PL - Netherlands TA - Cell Immunol JT - Cellular immunology JID - 1246405 RN - 0 (MIRN203 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Cell Line, Tumor MH - Dendritic Cells/*immunology MH - Exosomes/*immunology MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Interleukin-12/biosynthesis/immunology MH - MicroRNAs/genetics/*immunology MH - Pancreatic Neoplasms/genetics/*immunology MH - Toll-Like Receptor 4/genetics/*immunology MH - Tumor Necrosis Factor-alpha/biosynthesis/immunology OTO - NOTNLM OT - Dendritic cells OT - Exosomes OT - MicroRNAs OT - Pancreatic cancer OT - Toll-like receptor EDAT- 2014/10/08 06:00 MHDA- 2015/02/18 06:00 CRDT- 2014/10/08 06:00 PHST- 2014/07/05 00:00 [received] PHST- 2014/09/19 00:00 [revised] PHST- 2014/09/22 00:00 [accepted] PHST- 2014/10/08 06:00 [entrez] PHST- 2014/10/08 06:00 [pubmed] PHST- 2015/02/18 06:00 [medline] AID - S0008-8749(14)00147-6 [pii] AID - 10.1016/j.cellimm.2014.09.004 [doi] PST - ppublish SO - Cell Immunol. 2014 Nov-Dec;292(1-2):65-9. doi: 10.1016/j.cellimm.2014.09.004. Epub 2014 Sep 28.