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Genome-wide expression analysis demonstrates a dominant role of TLR4 for activation of human phagocytes by the alarmin MRP8 - GSE56681

Purpose

The alarmins myeloid-related protein (MRP) 8 and MRP14 are the dominant cytoplasmic proteins in phagocytes. After release by activated phagocytes extracellular MRP8/MRP14 complexes promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis or inflammatory bowel disease. As receptors for the pro-inflammatory effects of human MRP8, the active component of the MRP8/MRP14-complex, Toll-like receptor (TLR) 4 and the multi-ligand receptor of advanced glycation end products (RAGE) are controversial discussed. Using a comparative bioinformatics analysis between genome-wide response patterns of monocytes to MRP8, endotoxin and different cytokines we demonstrated a dominant role of TLR4 during MRP8-mediated phagocyte activation.

Hypothesis

TLR4 pathways plays an important role in the response to alarmin MRP8

Experimental Design

Human blood monocyte stimulated with various stimuli (control, MRP8, LPS, TNF, IL1) were selected for RNA extraction and hybridization on Affymetrix microarrays.

Experimental Variables

MRP8, LPS, TNF, IL1

Controls

Media

Methods

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Additional Information

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Microarray
Affymetrix HG-U133_Plus_2
19 Samples Loaded: 19
Human (Homo sapiens)
Monocytes
Healthy
Extraction of total RNA was performed with chaotropic ions and silica membran according to the manufacturer's instructions (Macherey-Nagel RNA isolation user manual).
Sample Set Spreadsheet
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Samples Preview
Sample ID Cell type Sample Title Treament
GSM1366783 human blood monocyte MS25_3_KO_1_091007 control
GSM1366784 human blood monocyte MS25_5_KO_1_091007 control
GSM1366785 human blood monocyte MS25_7_KO_1_091007 control
GSM1366786 human blood monocyte MS25_A_1_S100_A8_21.08_20071214 MRP8
GSM1366787 human blood monocyte MS25_B_2_S100_A8_29.08_20071214 MRP8
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File
GSE56681_ori.csv
Sample Set Spreadsheet
Log2 Transformed
Raw Signal
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Sample ID Cell type Sample Title Treament
GSM1366783
human blood monocyte
MS25_3_KO_1_091007
control
GSM1366784
human blood monocyte
MS25_5_KO_1_091007
control
GSM1366785
human blood monocyte
MS25_7_KO_1_091007
control
GSM1366786
human blood monocyte
MS25_A_1_S100_A8_21.08_20071214
MRP8
GSM1366787
human blood monocyte
MS25_B_2_S100_A8_29.08_20071214
MRP8
GSM1366788
human blood monocyte
MS25_C_3_S100_A8_12.09_20071214
MRP8
GSM1366789
human blood monocyte
MS25_Sample1_KO_5.6_20080819
control
GSM1366790
human blood monocyte
MS25_Sample2_TNF_alpha_5.6_20080819
TNF
GSM1366791
human blood monocyte
MS25_Sample3_IL1_beta_5.6_20080819
IL1b
GSM1366792
human blood monocyte
MS25_Sample4_TNF_alpha_30.5_20080819
TNF
GSM1366793
human blood monocyte
MS25_Sample5_IL1_beta_30.5_20080819
IL1b
GSM1366794
human blood monocyte
MS25_Sample6_TNF_alpha_13.6_20080819
TNF
GSM1366795
human blood monocyte
MS25_Sample7_IL1_beta_13.6_20080819
IL1b
GSM1366796
human blood monocyte
MS514_KO_020305_P4_260405
control
GSM1366797
human blood monocyte
MS514_KO_160205_P1_260405
control
GSM1366798
human blood monocyte
MS514_KO_160305_P7_260405
control
GSM1366799
human blood monocyte
MS514_LPS_020305_P5_260405
LPS
GSM1366800
human blood monocyte
MS514_LPS_160205_P2_260405
LPS
GSM1366801
human blood monocyte
MS514_LPS_160305_P8_260405
LPS

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