Journal of Multiple Sclerosis

Potential Roles of Prostaglandin E₂ and Interleukin-1? in Experimental Autoimmune Encephalomyelitis

Takako Takemiya

Multiple sclerosis (MS) is a progressive disease that is characterized by multifocal inflammation and demyelination in a central nervous system. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that shows ascending flaccid paralysis with inflammation of spinal cord. We focus on the potential roles of inducible prostaglandin E2 (PGE2) and interleukin-1β (IL-1β) in EAE after myelin oligodendrocyte glycoprotein 35-55 peptide immunization in this review. PGE2 synthesized by cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1) in vascular endothelial cells (VECs) or macrophages/microglia aggravates inflammation, demyelination and paralysis and facilitates the activation and differentiation of CD4-positive (CD4+) T cells into interleukin-17 (IL-17)-producing helper T cells to promote neuronal dysfunction and blood-spinal cord barrier disruption in the EAE model. PGE2 also causes vascularity and increases IL-1β production in VECs and CD4+ T cells, and IL-1β plays a crucial role in facilitating EAE progression and stimulates the synthesis of COX-2 and mPGES-1 to produce PGE2. Thus, the
local PGE2-IL-1ββ-PGE2 signalling pathway facilitates IL-17 production in inflammatory lesions in the spinal cord of EAE animals. This pathway represents a possible mechanism by which PGE2 participates in EAE pathology. Taken together, this evidence highlights the intercellular PGE2 signalling pathway in the spinal cord as a therapeutic target for ameliorating MS severity after disease onset.