title: PKR mediated regulation of inflammation and IL-10 during viral encephalomyelitis.
abstract: Double-stranded RNA-dependent protein kinase (PKR) regulates antiviral activity, immune responses, apoptosis and neurotoxicity. Gliatropic coronavirus infection induced PKR activation in infected as well uninfected cells within the central nervous system (CNS). However, PKR deficiency only modestly increased viral replication and did not affect IFN-α/β or IL-1β expression. Despite reduced Il-6, Ccl5, and Cxcl10 mRNA, protein levels remained unaltered. Furthermore, PKR deficiency selectively reduced IL-10 production in CD4, but not CD8 T cells, without affecting CNS pathology. The results demonstrate the ability of PKR to balance neuroinflammation by selectively modulating key cytokines and chemokines in CNS resident and CD4 T cells.
authors.affiliation: Department of Neurosciences, NC-30, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Kapil
authors.affiliation: Department of Neurosciences, NC-30, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stohlman
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Hinton
authors.affiliation: Department of Neurosciences, NC-30, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Electronic address: bergmac@ccf.org.
authors.forename: Cornelia C
authors.initials: CC
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology* / Q000378:metabolism; D018792:Encephalitis, Viral / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D019892:eIF-2 Kinase / Q000276:immunology* / Q000378:metabolism
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10; D019892:eIF-2 Kinase
keywords: CD4 T cells; Coronavirus; Encephalomyelitis; IL-10; Protein kinase RNA-dependent (PKR)