Possible involvement of kinin B1 receptor in the development of experimental autoimmune encephalomyelitis in rats

• Autorzy: Podsiadlo K. , Dabrowska-Bouta B. , Sulkowski G. , Struzynska L.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Experimental autoimmune encephalomyelitis (EAE) is the most commonly used animal model of multiple sclerosis (MS) which is neuroinflammatory demyelinating disease of autoimmune origin. Among inflammatory mediators, kinins are bioactive peptides critically involved in regulation of the inflammatory response and vascular permeability. These biological activities of kinins are mediated by B1 receptors through the release of pro-inflammatory cytokines. AIM(S): Therefore, there are reasons to investigate the role of B1 receptor in the enhancement of the BBB permeability during development of EAE. METHOD(S): Group of female Lewis rats was immunized by intradermal injection of 100 μl inoculum. The second group was injected i.p. with DALBK (B1R antagonist) after immunization. Control group was not immunized. Animals were sacrificed in different stages of the disease. Parts of brains were used for Western blotting analysis and measurement of inflammatory cytokines using RayBio Rat Cytokine Antibody Array (RayBiotech, Inc.). Immunohistochemical study on isolated fraction of microvessels was also performed. Gene expression was quantified by RT-PCR RESULTS: We noticed the increased expression of B1R in rat brain and isolated fraction of microvessels in the symptomatic phase of EAE. Animals treated with DALBK exhibited improvement of neurological symptoms and decreased overexpression of B1R. We also noticed increased protein level of chemokines and proinflammatory cytokines. Using a confocal microscope, we observed lowered immunoreactivity of thight junctions proteins (ZO-1, occludin, claudin 5) and pericytes markers (PDGFβR and angiopoietin‑1) in microvessels’ fraction obtained from EAE rats which increased after DALBK. CONCLUSIONS: Administration of kinin B1 receptor antagonist (DALBK) significantly improved the condition of animals. Results show that B1R‑mediated pro‑inflammatory effect of kinins may be involved in pathomechanisms operating during EAE which may lead to enhanced permeability of microvessels.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.104-105

Twórcy

autor

Podsiadlo K.

• Department of Neurochemistry, Laboratory of Pathoneurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Dabrowska-Bouta B.

• Department of Neurochemistry, Laboratory of Pathoneurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Sulkowski G.

• Department of Neurochemistry, Laboratory of Pathoneurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Struzynska L.

• Department of Neurochemistry, Laboratory of Pathoneurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland