title: Additive effect of prostaglandin E2 and adenosine in mouse experimental autoimmune encephalomyelitis.
abstract: 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 E (PGE) and adenosine play important roles in immune inflammation although the mechanism remains unclear. In the study, we examined individual and combined effect of PGE and adenosine during EAE development. The results showed that both PGE 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 PGE and adenosine receptors indicated that the suppression of EAE development was mainly mediated by EP4 and A receptors. Furthermore, combined PGE and adenosine treatment significantly suppressed the production of IFN-γ and IL-17 via EP4 and A receptors. Taken together, PGE and adenosine in combination could protect EAE mouse from serious EAE through limiting the over-reactive effects of T cells via EP4 and A receptors.
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai 200032, China.
authors.forename: JingJing
authors.initials: J
authors.lastname: Xu
authors.forename: Si
authors.initials: S
authors.lastname: Guo
authors.forename: ZhanKui
authors.initials: Z
authors.lastname: Jia
authors.forename: ShengLi
authors.initials: S
authors.lastname: Ma
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Xue
mesh_terms: D000241:Adenosine / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D043705:Receptor, Adenosine A2A / Q000276:immunology / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D020381:Interleukin-17; D043705:Receptor, Adenosine A2A; D058309:Receptors, Prostaglandin E, EP4 Subtype; D007371:Interferon-gamma; D000241:Adenosine; D015232:Dinoprostone