The scope and activation mechanisms of chemokine gene expression in primary astrocytes following infection with Theiler's virus.
Intracerebral infection with Theiler's virus induces a demyelinating disease that resembles human MS. In order to delineate the early events in virus-induced inflammatory disease, we have analyzed chemokine gene activation following Theiler's murine encephalomyelitis virus (TMEV) infection. Infection of primary astrocyte cultures results in activation of various chemokine genes (GRO-1, MCP-1, MCP-5, MIP-1alpha, MIP-1beta, MIP-2, RANTES, IP-10 and MCP-3) that are important in the initiation of an inflammatory response. As early as 1-3 h after TMEV infection, chemokine gene expression is strongly activated. In addition, proinflammatory cytokines do not interfere with TMEV-induced chemokine gene expression and some cytokines may function synergistically for virus-induced upregulation of chemokine gene expression. Chemokine gene activation by TMEV appears to be largely independent of the IFNalphabeta pathway and partly dependent on dsRNA-dependent protein kinase (PKR) and MAP kinase pathways. However, TMEV-induced chemokine gene expression is completely dependent on the NFkappaB pathway. These results strongly suggest that the expression of select chemokine genes upon TMEV infection is activated via the NFkappaB pathway, similar to that of proinflammatory cytokine genes, and these cellular gene products appear to synergistically promote inflammatory responses in the CNS.
Palma
JoAnn P
JP
Department of Microbiology-Immunology, Northwestern University Feinberg Medical School, 303 E. Chicago Ave., Chicago, IL 60611, USA.
Kim
Byung S
BS
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D007239:Infections / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017471:Receptors, Interferon / Q000235:genetics; D017945:Theilovirus / Q000502:physiology*; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection / Q000379:methods; D000097782:NF-kappaB-Inducing Kinase
D018925:Chemokines; D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D017471:Receptors, Interferon; D000097782:NF-kappaB-Inducing Kinase