Chemokine expression in GKO mice (lacking interferon-gamma) with experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) considered to be an animal model for multiple sclerosis (MS). The detailed mechanism that specifies accumulation of inflammatory cells within the CNS in these conditions remains a subject of active investigation. Chemokines including IP-10, GRO-alpha, MCP-1 are produced in EAE tissues selectively by parenchymal astrocytes, but the regulatory stimuli that govern this expression remain undetermined. The unexpected occurrence of increased EAE susceptibility in Balb/c GKO mice (lacking IFN-gamma) offered an opportunity to examine the spectrum of chemokine expression during immune-mediated inflammation in the absence of a single regulatory cytokine. We found that chemokines MCP-1 and GRO-alpha were upregulated in the CNS of mice with EAE despite the GKO genotype. IP-10, which is highly expressed in the CNS of mice with an intact IFN-gamma gene and EAE, was strikingly absent. In vitro experiments confirmed that IFNgamma selectively stimulates astrocytes for IP-10 expression. These results indicate that IP-10 is dependent upon IFN-gamma for its upregulation during this model disease, and document directly that astrocyte expression of chemokines during EAE is governed by pro-inflammatory cytokines.
Glabinski
A R
AR
Department of Neurosciences, The Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
Krakowski
M
M
Han
Y
Y
Owens
T
T
Ransohoff
R M
RM
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002417:Cattle; D002490:Central Nervous System / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors
C475896:CXCL1 protein, Bos taurus; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma