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Series GSE39745 Query DataSets for GSE39745
Status Public on May 03, 2013
Title Human monocyte-derived dendritic cells treated with U0126 or SB203580
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Identification of MEK-ERK or p38MAPK dependent genes in human monocyte derived dendritic cells.
Dendritic cells (DC) promote tolerance or immunity depending on their maturation state. Previous studies have revealed that DC maturation is enhanced or accelerated upon MEK-ERK signaling pathway inhibition. We have now determined the contribution of MEK-ERK activation to the profile of gene expression of human immature monocyte-derived dendritic cells (MDDC) and peripheral blood myeloid DC. ERK inhibition altered the expression of genes that mediate CCL19-directed migration (CCR7) and LDL binding (CD36, SCARB1, OLR1, CXCL16) by immature DC. Besides, ERK upregulated CCL2 expression while impaired the expression of DC maturation markers (RUNX3, ITGB7, IDO1). MEK-ERK-regulated genes exhibited an over-representation of cognate sequences for the Aryl Hydrocarbon Receptor (AhR) transcription factor, and we show that AhR mediates some of the ERK-dependent transcriptional effects in DC. Therefore, MEK-ERK signaling pathway regulates antigen capture, lymph node homing and the acquisition of maturation-associated genes, and its contribution to the maintenance of the immature state of MDDC and myeloid DC is partly dependent on the activity of AhR. Since pharmacological modulation of the MEK-ERK signaling pathway has been proposed as a potential therapeutic strategy for cancer, our findings indicate that ERK inhibitors might influence the generation of anti-tumor responses through regulation of critical DC effector functions.
Overall design Human peripheral blood monocytes from three independent healthy donors (DC4, DC5 and DC7) were isolated by anti-CD14-labeled magnetic microbeads. CD14+ monocytes were cultured for 5 days in RPMI 10% FCS containing GM-CSF and IL-4 to generate immature monocyte-derived dendritic cells (MDDC). Immature MDDC were exposed to MEK inhibitor, U0126, or p38MAPK inhibitor, SB203580 for 1 hour and a final dose of GM-CSF and IL-4 were added to the culture. Cells were collected for analysis after 4, 10 or 24 hours.Total RNA from each condition was extracted using the All prep DNA/RNA/protein mini kit (Qiagen) and hybridized to an Agilent Human Whole Genome (4x44) Oligo Microarray. All experimental procedures were performed following manufacturer instructions.
Contributor(s) Corbi AL, Aguilera-Montilla N
Citation(s) 23430108
Submission date Jul 30, 2012
Last update date Feb 22, 2018
Contact name Angel L CorbĂ­
Phone 34 918373112
Organization name Consejo Superior de Investigaciones CientĂ­ficas
Department Molecular Microbiology and Infection Biology
Lab Myeloid Cell Laboratory
Street address Ramiro de Maeztu 9
City Madrid
State/province Madrid
ZIP/Postal code 28040
Country Spain
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (35)
GSM978432 Immature MDDC_DMSO 4h_ replicate 1
GSM978433 Immature MDDC_DMSO 4h_ replicate 2
GSM978434 Immature MDDC_DMSO 4h_ replicate 3
BioProject PRJNA171700

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Supplementary file Size Download File type/resource
GSE39745_RAW.tar 77.6 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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