Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4+ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis

• Main Authors: Takako Takemiya, Chisen Takeuchi, Marumi Kawakami
• Format: Article
• Language: English
• Published: MDPI AG 2017-12-01
• Series: International Journal of Molecular Sciences
• Subjects: 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)
• Online Access: https://www.mdpi.com/1422-0067/18/12/2758

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.