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Series GSE60824 Query DataSets for GSE60824
Status Public on Oct 01, 2014
Title IL-17A influences essential functions of the monocyte / macrophage lineage and is involved in advanced murine and human atherosclerosis
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. Interleukin-17A is a pro-inflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. 26-weeks old apolipoprotein E-deficient (Apoe-/-) mice were fed a standard chow diet and treated either with IL-17A mAb (n=15) or irrelevant immunoglobulin (n=10) for 16 weeks. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (P=0.001) by reducing inflammatory burden and cellular infiltration (P=0.01) and improved lesion stability (P=0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, sensitization of antigen-presenting cells toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a pro-inflammatory milieu and up-regulation of molecules expressed by the IL-17A-induced macrophage subtype. We here show for the first time that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in Apoe-/- mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte / macrophage lineage. In addition, translational experiments underline the relevance for the human system.
 
Overall design Effects of IL-17A on human monocyte-derived macrophages were assessed (n=2 per group).
 
Contributor(s) Erbel C, Gleissner C
Citation(s) 25261478
Submission date Aug 27, 2014
Last update date Feb 18, 2019
Contact name Christian Albert Gleissner
E-mail(s) gleissner.christian@rottalinnkliniken.de
Phone +49-8721-9837302
Organization name Rottal-Inn Kliniken KU
Department Cardiology
Lab Gleissner
Street address Simonsöder Allee 20
City Eggenfelden
ZIP/Postal code 84307
Country Germany
 
Platforms (1)
GPL6884 Illumina HumanWG-6 v3.0 expression beadchip
Samples (4)
GSM1489479 Control 1
GSM1489480 Control 2
GSM1489481 IL-17A 1
Relations
BioProject PRJNA259626

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60824_Normalized_data_with_gene_annotations.txt.gz 668.1 Kb (ftp)(http) TXT
GSE60824_RAW.tar 43.5 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data are available on Series record

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