Dynamic regulation of alpha- and beta-chemokine expression in the central nervous system during mouse hepatitis virus-induced demyelinating disease.
Infection of C57BL/6 mice with the V5A13.1 strain of mouse hepatitis virus (MHV-V5A13.1) results in an acute encephalomyelitis and chronic demyelinating disease with features similar to the human demyelinating disease multiple sclerosis. Chemokines are a family of proinflammatory cytokines associated with inflammatory pathology in various diseases. The kinetics and histologic localization of chemokine production in the central nervous system of MHV-infected mice were examined to identify chemokines that contribute to inflammation and demyelination. Transcripts for the chemokines cytokine-response gene-2 (CRG-2), regulated on activation, normal T cell expressed and secreted (RANTES), macrophage-chemoattractant protein-1 and protein-3 (MCP-1, MCP-3), macrophage-inflammatory protein-1beta (MIP-1beta), and MIP-2 were detected in the brains of MHV-infected mice at 3 days postinfection (p.i.), and these transcripts were increased markedly in brains and spinal cords at day 7 p.i., which coincides with the occurrence of acute viral encephalomyelitis. By day 35 p.i., RANTES, CRG-2, and MIP-1beta were detected in brains and spinal cords of mice with chronic demyelination. CRG-2 mRNA expression colocalized with viral RNA and was associated with demyelinating lesions. Astrocytes were the predominant cell type expressing CRG-2 mRNA. These observations suggest a role for chemokines, notably CRG-2, in the initiation and maintenance of an inflammatory response following infection with MHV, which is important in contributing to demyelination.
Lane
T E
TE
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. tlane@scripps.edu
Asensio
V C
VC
Yu
N
N
Paoletti
A D
AD
Campbell
I L
IL
Buchmeier
M J
MJ
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis*; D018352:Coronavirus Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003711:Demyelinating Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018792:Encephalitis, Viral / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000096:biosynthesis; D006517:Murine hepatitis virus; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism*
D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; D015846:Monokines