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Open AccessArticle

Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1β in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis

1
Medical Research Institute, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
2
Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, Tokyo 114-0033, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3647; https://doi.org/10.3390/ijms19113647
Received: 30 September 2018 / Revised: 10 November 2018 / Accepted: 14 November 2018 / Published: 19 November 2018
(This article belongs to the Special Issue New Molecular Mechanisms in Multiple Sclerosis)
Microsomal prostaglandin E synthetase-1 (mPGES-1) is an inducible terminal enzyme for the production of prostaglandin E2 (PGE2). In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mPGES-1 is induced in vascular endothelial cells (VECs) around inflammatory foci and facilitates inflammation, demyelination, and paralysis. Therefore, we investigated the role of CD31-positive VECs in mPGES-1-mediated EAE aggravation using immunohistochemical analysis and imaging of wild-type (wt) and mPGES-1-deficient (mPGES-1−/−) mice. We demonstrated that EAE induction facilitated vascularity in inflammatory lesions in the spinal cord, and this was significantly higher in wt mice than in mPGES-1−/− mice. In addition, endothelial interleukin-1β (IL-1β) production was significantly higher in wt mice than in mPGES-1−/− mice. Moreover, endothelial PGE2 receptors (E-prostanoid (EP) receptors EP1–4) were expressed after EAE induction, and IL-1β was induced in EP receptor-positive VECs. Furthermore, IL-1 receptor 1 expression on VECs was increased upon EAE induction. Thus, increased vascularity is one mechanism involved in EAE aggravation induced by mPGES-1. Furthermore, mPGES-1 facilitated the autocrine function of VECs upon EP receptor induction and IL-1β production, modulating mPGES-1 induction in EAE. View Full-Text
Keywords: vascular endothelial cells; microsomal prostaglandin E synthetase-1; interleukin-1β; prostaglandin E2; experimental autoimmune encephalomyelitis; multiple sclerosis vascular endothelial cells; microsomal prostaglandin E synthetase-1; interleukin-1β; prostaglandin E2; experimental autoimmune encephalomyelitis; multiple sclerosis
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Takemiya, T.; Kawakami, M.; Takeuchi, C. Endothelial Microsomal Prostaglandin E Synthetase-1 Upregulates Vascularity and Endothelial Interleukin-1β in Deteriorative Progression of Experimental Autoimmune Encephalomyelitis. Int. J. Mol. Sci. 2018, 19, 3647.

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