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Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system

Item Type:Article
Title:Role of the renin-angiotensin system in autoimmune inflammation of the central nervous system
Creators Name:Stegbauer, J. and Lee, D.H. and Seubert, S. and Ellrichmann, G. and Manzel, A. and Kvakan, H. and Mueller, D.N. and Gaupp, S. and Rump, L.C. and Gold, R. and Linker, R.A.
Abstract:Angiotensin II is the principle effector molecule of the renin angiotensin system (RAS). It exerts its various actions on the cardiovascular and renal system, mainly via interaction with the angiotensin II type-1 receptor (AT1R), which contributes to blood pressure regulation and development of hypertension but may also mediate effects on the immune system. Here we study the role of the RAS in myelin-oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE), a model mimicking many aspects of multiple sclerosis. Quantitative RT-PCR analyses showed an up-regulation of renin, angiotensin-converting enzyme, as well as AT1R in the inflamed spinal cord and the immune system, including antigen presenting cells (APC). Treatment with the renin inhibitor aliskiren, the angiotensin II converting-enzyme inhibitor enalapril, as well as preventive or therapeutic application of the AT1R antagonist losartan, resulted in a significantly ameliorated course of MOG-EAE. Blockade of AT1R did not directly impact on T-cell responses, but significantly reduced numbers of CD11b(+) or CD11c(+) APC in immune organs and in the inflamed spinal cord. Additionally, AT1R blockade impaired the expression of CCL2, CCL3, and CXCL10, and reduced CCL2-induced APC migration. Our findings suggest a pivotal role of the RAS in autoimmune inflammation of the central nervous system and identify RAS blockade as a potential new target for multiple sclerosis therapy.
Keywords:Antigen Presenting Cell, Blood Pressure, Chemokine, Multiple Sclerosis, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:106
Number:35
Page Range:14942-14947
Date:1 September 2009
Official Publication:https://doi.org/10.1073/pnas.0903602106
PubMed:View item in PubMed

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