The Role of Kinin Receptors in Preventing Neuroinflammation and Its Clinical Severity during Experimental Autoimmune Encephalomyelitis in Mice
Open Access
- 22 November 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (11), e27875
- https://doi.org/10.1371/journal.pone.0027875
Abstract
Multiple sclerosis (MS) is a demyelinating and neuroinflammatory disease of the human central nervous system (CNS). The expression of kinins is increased in MS patients, but the underlying mechanisms by which the kinin receptor regulates MS development have not been elucidated. Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice by immunization with MOG35–55 peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Here, we report that blockade of the B1R in the induction phase of EAE markedly suppressed its progression by interfering with the onset of the immune response. Furthermore, B1R antagonist suppressed the production/expression of antigen-specific TH1 and TH17 cytokines and transcription factors, both in the periphery and in the CNS. In the chronic phase of EAE, the blockade of B1R consistently impaired the clinical progression of EAE. Conversely, administration of the B1R agonist in the acute phase of EAE suppressed disease progression and inhibited the increase in permeability of the blood-brain barrier (BBB) and any further CNS inflammation. Of note, blockade of the B2R only showed a moderate impact on all of the studied parameters of EAE progression. Our results strongly suggest that kinin receptors, mainly the B1R subtype, play a dual role in EAE progression depending on the phase of treatment through the lymphocytes and glial cell-dependent pathways.This publication has 55 references indexed in Scilit:
- Anti‐nociceptive effect of kinin B1 and B2 receptor antagonists on peripheral neuropathy induced by paclitaxel in miceBritish Journal of Pharmacology, 2011
- Inhibitor of PI3Kγ ameliorates TNBS‐induced colitis in mice by affecting the functional activity of CD4+CD25+FoxP3+ regulatory T cellsBritish Journal of Pharmacology, 2011
- Isolation rearing-induced deficits in contextual fear learning do not require CRF2 receptorsBehavioural Brain Research, 2010
- Autoimmune T cell responses in the central nervous systemNature Reviews Immunology, 2009
- A cellular model of Alzheimer's disease therapeutic efficacy: PKC activation reverses Aβ-induced biomarker abnormality on cultured fibroblastsNeurobiology of Disease, 2009
- Localizing central nervous system immune surveillance: Meningeal antigen‐presenting cells activate T cells during experimental autoimmune encephalomyelitisAnnals of Neurology, 2009
- Kinin B2receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in miceJournal of Neuroinflammation, 2008
- Differential regulation of central nervous system autoimmunity by TH1 and TH17 cellsNature Medicine, 2008
- Multiple sclerosis: a complicated picture of autoimmunityNature Immunology, 2007
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001