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Blockade of the kinin B1 receptor affects the cytokine/chemokine profile in rat brain subjected to autoimmune encephalomyelitis

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Abstract

Kinins are bioactive peptides which provide multiple functions, including critical regulation of the inflammatory response. Released during tissue injury, kinins potentiate the inflammation which represents a hallmark of numerous neurological disorders, including those of autoimmune origin such as multiple sclerosis (MS). In the present work, we assess the expression of B1 receptor (B1R) in rat brain during the course of experimental autoimmune encephalomyelitis (EAE) which is an animal model of MS. We apply pharmacological inhibition to investigate the role of this receptor in the development of neurological deficits and in shaping the cytokine/chemokine profile during the course of the disease. Overexpression of B1R is observed in brain tissue of rats subjected to EAE, beginning at the very early asymptomatic phase of the disease. This overexpression is suppressed by a specific antagonist known as DALBK. The involvement of B1R in the progression of neurological symptoms in immunized rats is confirmed. Analysis of an array of cytokines/chemokines identified a sub-group as being B1R-dependent. Increase of the protein levels for the proinflammatory cytokines (Il-6, TNF-α but not IL-1β), chemokines attracting immune cells into nervous tissue (MCP-1, MIP-3α, LIX), and protein levels of fractalkine and vascular endothelial growth factor observed in EAE rats, were significantly diminished after DALBK administration. This may indicate the protective potential of pharmacological inhibition of B1R. However, simultaneously reduced protein levels of anti-inflammatory and neuroprotective factors (IL-10, IL-4, and CNTF) was noticed. The results show that B1R-mediated signaling regulates the cellular response profile following neuroinflammation in EAE.

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Acknowledgements

This work was supported by funds from the Polish Ministry of Scientific Research and Higher Education for the KNOW-MMRC project.

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  1. Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 A. Pawińskiego str., 02-106, Warsaw, Poland

    Karolina Podsiadło, Grzegorz Sulkowski, Beata Dąbrowska-Bouta & Lidia Strużyńska

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  1. Karolina Podsiadło
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  2. Grzegorz Sulkowski
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  3. Beata Dąbrowska-Bouta
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Correspondence to Lidia Strużyńska.

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Podsiadło, K., Sulkowski, G., Dąbrowska-Bouta, B. et al. Blockade of the kinin B1 receptor affects the cytokine/chemokine profile in rat brain subjected to autoimmune encephalomyelitis. Inflammopharmacol 25, 459–469 (2017). https://doi.org/10.1007/s10787-017-0312-9

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