Next Article in Journal
Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment
Next Article in Special Issue
Twelve Weeks of Medium-Intensity Exercise Therapy Affects the Lipoprotein Profile of Multiple Sclerosis Patients
Previous Article in Journal
Galectin-7 in Epithelial Homeostasis and Carcinomas
Previous Article in Special Issue
The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(12), 2758; doi:10.3390/ijms18122758

Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4+ T Cells through IL-1β Autocrine Function in 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.
Received: 20 October 2017 / Revised: 9 December 2017 / Accepted: 13 December 2017 / Published: 19 December 2017
(This article belongs to the Special Issue Advances in Multiple Sclerosis 2017)
View Full-Text   |   Download PDF [4307 KB, uploaded 21 December 2017]   |  

Abstract

Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E2 (PGE2). In our previous study, we investigated the role of mPGES-1 in the inflammation and demyelination observed in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, using mPGES-1-deficient (mPGES-1−/−) and wild-type (wt) mice. We found that mPGES-1 facilitated inflammation, demyelination, and paralysis and was induced in vascular endothelial cells and macrophages and microglia around inflammatory foci. Here, we investigated the role of interleukin-1β (IL-1β) in the intercellular mechanism stimulated by mPGES-1 in EAE spinal cords in the presence of inflammation. We found that the area invaded by CD4-positive (CD4+) T cells was extensive, and that PGE2 receptors EP1–4 were more induced in activated CD4+ T cells of wt mice than in those of mPGES-1−/− mice. Moreover, IL-1β and IL-1 receptor 1 (IL-1r1) were produced by 65% and 48% of CD4+ T cells in wt mice and by 44% and 27% of CD4+ T cells in mPGES-1−/− mice. Furthermore, interleukin-17 (IL-17) was released from the activated CD4+ T cells. Therefore, mPGES-1 stimulates an intercellular interaction between CD4+ T cells by upregulating the autocrine function of IL-1β in activated CD4+ T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice. View Full-Text
Keywords: interleukin-1β (IL-1β); prostaglandin E2 (PGE2); microsomal prostaglandin synthetase-1 (mPGES-1); mPGES-1-deficient (mPGES-1−/−) mice; CD4-positive T cells (CD4+ T cells); interleukin-17 (IL-17); experimental allergic encephalomyelitis (EAE); multiple sclerosis (MS); vascular endothelial cells (VECs); myelin oligodendrocyte glycoprotein35–55 peptide (MOG35–55) interleukin-1β (IL-1β); prostaglandin E2 (PGE2); microsomal prostaglandin synthetase-1 (mPGES-1); mPGES-1-deficient (mPGES-1−/−) mice; CD4-positive T cells (CD4+ T cells); interleukin-17 (IL-17); experimental allergic encephalomyelitis (EAE); multiple sclerosis (MS); vascular endothelial cells (VECs); myelin oligodendrocyte glycoprotein35–55 peptide (MOG35–55)
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Takemiya, T.; Takeuchi, C.; Kawakami, M. Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4+ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis. Int. J. Mol. Sci. 2017, 18, 2758.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top