title: Immunoregulatory function of bone marrow mesenchymal stem cells in EAE depends on their differentiation state and secretion of PGE2.
abstract: Bone marrow mesenchymal stem cells (BMSC)-induced amelioration of experimental autoimmune encephalomyelitis (EAE) was diminished with neuronal differentiantion of BMSC (nBMSC). BMSC secreted large amounts of PGE2, compared to nBMSC, which correlated with higher efficacy to EAE inhibition. EAE mice treated with PGE2 inhibitor, meloxicam showed decreased serum levels of PGE2 and in parallel decreased inhibitory effect on EAE course. In addition, high levels of PGE2 secretion correlated with high expression of indoleamine-2,3-dioxygenase (IDO). Meloxicam blocked IDO expression in BMSC transferred mice indicating functional relation between PGE2 and IDO induction. The current findings demonstrates PGE2 involvement in BMSC-induced inhibition of EAE and provides a mechanistic link between BMSC-derived PGE2 and IDO-dependent immunoregulation of this autoimmune condition.
authors.affiliation: Department of Neurology, Medical University of Lodz, Lodz, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Matysiak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Orlowski
authors.forename: Maria
authors.initials: M
authors.lastname: Fortak-Michalska
authors.forename: Anna
authors.initials: A
authors.lastname: Jurewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D005260:Female; D056747:Immunomodulation / Q000276:immunology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D000077239:Meloxicam; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D013843:Thiazines; D013844:Thiazoles; D015232:Dinoprostone; D000077239:Meloxicam