title: IL-17A activates ERK1/2 and enhances differentiation of oligodendrocyte progenitor cells.
abstract: Inflammatory signals present in demyelinated multiple sclerosis lesions affect the reparative remyelination process conducted by oligodendrocyte progenitor cells (OPCs). Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 have differing effects on the viability and growth of OPCs, however the effects of IL-17A are largely unknown. Primary murine OPCs were stimulated with IL-17A and their viability, proliferation, and maturation were assessed in culture. IL-17A-stimulated OPCs exited the cell cycle and differentiated with no loss in viability. Expression of the myelin-specific protein, proteolipid protein, increased in a cerebellar slice culture assay in the presence of IL-17A. Downstream, IL-17A activated ERK1/2 within 15 min and induced chemokine expression in 2 days. These results demonstrate that IL-17A exposure stimulates OPCs to mature and participate in the inflammatory response.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611; Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Rodgers
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Robinson
authors.forename: Elen S
authors.initials: ES
authors.lastname: Rosler
authors.forename: Karen
authors.initials: K
authors.lastname: Lariosa-Willingham
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Persons
authors.forename: Jason C
authors.initials: JC
authors.lastname: Dugas
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology*; D005434:Flow Cytometry; D005620:Freund's Adjuvant / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018991:Myelin Proteolipid Protein / Q000235:genetics; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009836:Oligodendroglia / Q000187:drug effects* / Q000201:enzymology*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000633:toxicity; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: D016207:Cytokines; C491673:Il17ra protein, mouse; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C047516:Plp1 protein, mouse; D053722:Receptors, Interleukin-17; C445081:myelin oligodendrocyte glycoprotein (35-55); D049452:Green Fluorescent Proteins; D005620:Freund's Adjuvant
keywords: ERK; chemokine; inflammation; interleukin-17; myelin; oligodendrocyte