Influence of DALBK-an antagonist of kinin receptor B1R-on the course of experimental autoimmune encephalomyelitis in rats

• Autorzy: Podsiadlo K. , Grygorowicz T. , Struzynska L.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Experimental autoimmune encephalomyelitis (EAE) has been used for several decades as an animal model of multiple sclerosis (MS), an inflammatory demyelinating disease. According to the previous studies mammalian central nervous system presents all components of the kallikrein-kinin system. Biological activity of kinin is mediated by two types of G proteinbound receptors – B1 and B2. Therefore, there are reasons to investigate the participation of B1 receptor in enhancement of the BBB permeability during development of EAE. METHODS: One group of female Lewis rats was immunized by intradermal injection. The second group was injected ip with DALBK (B1R antagonist) after immunization. Control group was not immunized. Rats were monitored daily for clinical signs and loss of weight. Animals were sacrificed in different stages of the disease. Parts of brains were used for Western blotting analysis. Immunohistochemical study was also performed. RESULTS: We noticed the increased level of B1R protein in rat brain in the symptomatic phase of EAE. Animals treated with DALKB exhibited improvement of neurological symptoms and decreased level of B1R protein in most cases. Using a confocal microscope we assessed immunoreactivity of B1R and markers of individual components of glio-vascular unit (astrocytes, endothelial cells and pericytes). We also noticed changes in the level of astroglial markers GFAP and AQP4 during EAE, so as decreased expression of thight jounctions proteins (ZO-1, Occludin, Claudin 5), which were partially abolished by DALBK. CONCLUSIONS: Administration of kinin B1 receptor antagonist (DALBK) significantly improved the condition of animals by reducing the proinflammatory effects of kinins. The results show that the kinin receptor B1 may play a role in pathomechanisms operating during the course of EAE and appears to be a potential therapeutic target. This work was supported by funds from KNOW 2013-2017 project.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S68

Twórcy

autor

Podsiadlo K.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Grygorowicz T.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Struzynska L.

• Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland