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

Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E-2 (PGE(2)). 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-1 beta (IL-1 beta) 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 PGE(2) receptors EP1-4 were more induced in activated CD4(+) T cells of wt mice than in those of mPGES-1(-/-) mice. Moreover, IL-1 beta 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-1 beta in activated CD4(+) T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice.