Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality

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Item Type:	Article
Title:	Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality
Creators Name:	Virgili, N., Mancera, P., Chanvillard, C., Wegner, A., Wappenhans, B., Rodríguez, M.J., Infante-Duarte, C., Espinosa-Parrilla, J.F. and Pugliese, M.
Abstract:	Activation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated as an effective mechanism to confer cardio and neuroprotection, especially in situations associated to oxidative stress. Pharmacological activation of these channels inhibits glia-mediated neuroinflammation. In this way, diazoxide, an old-known mitochondrial KATP channel opener, has been proposed as an effective and safe treatment for different neurodegenerative diseases, demonstrating efficacy in different animal models, including the experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis. Although neuroprotection and modulation of glial reactivity could alone explain the positive effects of diazoxide administration in EAE mice, little is known of its effects on the immune system and the autoimmune reaction that triggers the EAE pathology. The aim of the present work was to study the effects of diazoxide in autoimmune key processes related with EAE, such as antigen presentation and lymphocyte activation and proliferation. Results show that, although diazoxide treatment inhibited in vitro and ex-vivo lymphocyte proliferation from whole splenocytes it had no effect in isolated CD4(+) T cells. In any case, treatment had no impact in lymphocyte activation. Diazoxide can also slightly decrease CD83, CD80, CD86 and major histocompatibility complex class II expression in cultured dendritic cells, demonstrating a possible role in modulating antigen presentation. Taken together, our results indicate that diazoxide treatment attenuates autoimmune encephalomyelitis pathology without immunosuppressive effect.
Keywords:	Diazoxide, K(ATP) Channels, EAE Mice, Spleen, Lymphocyte, Dendritic Cell
Source:	Journal of Neuroimmune Pharmacology
ISSN:	1557-1890
Publisher:	Springer
Volume:	9
Number:	4
Page Range:	558-568
Date:	September 2014
Official Publication:	https://doi.org/10.1007/s11481-014-9551-3
PubMed:	View item in PubMed

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