Additive effect of prostaglandin E2 and adenosine in mouse experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), which is a T cell-mediated autoimmune disease of the central nervous system (CNS). Emerging evidence indicates that both prostaglandin E2 (PGE2) and adenosine play important roles in immune inflammation although the mechanism remains unclear. In the study, we examined individual and combined effect of PGE2 and adenosine during EAE development. The results showed that both PGE2 and adenosine could inhibit EAE progression and they in combination showed substantially higher inhibition than each modality used alone. On the other hand, using specific agonists or antagonists for PGE2 and adenosine receptors indicated that the suppression of EAE development was mainly mediated by EP4 and A2A receptors. Furthermore, combined PGE2 and adenosine treatment significantly suppressed the production of IFN-γ and IL-17 via EP4 and A2A receptors. Taken together, PGE2 and adenosine in combination could protect EAE mouse from serious EAE through limiting the over-reactive effects of T cells via EP4 and A2A receptors.

► PGE2 and adenosine directly inhibit the development of EAE.
► Cooperation of PGE2 and adenosine can ameliorate severity of EAE than used alone.
► Cooperation of PGE2 and adenosine can inhibit cytokine production of T cells.
► The cooperative actions of PGE2 and adenosine are mediated via EP4 and A2A.