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| 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
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| 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.
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| Overall design |
Effects of IL-17A on human monocyte-derived macrophages were assessed (n=2 per group).
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| 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 |
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| Platforms (1) |
| GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA259626 |
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