Subsequent to demyelination in multiple sclerosis, myelin repair occurs but, as lesions age, the ability to remyelinate diminishes. Molecular pathways underl ying oligodendrocyte behaviour during CNS remyelination rem...Subsequent to demyelination in multiple sclerosis, myelin repair occurs but, as lesions age, the ability to remyelinate diminishes. Molecular pathways underl ying oligodendrocyte behaviour during CNS remyelination remain to be elucidated. In this study, we report for the first time constitutive expression of the CXC/ α chemokine receptors, CXCR1, CXCR2 and CXCR3, on oligodendrocytes in normal a dult human CNS tissue, the levels of which were upregulated in multiple sclerosi s and other neurological diseases (OND). In addition, both immature (A2B5+ /O4 + ) and more mature (CNPase+ ) human oligodendrocytes in vitro expressed the s ame three receptors. The respective ligands to CXCR1, CXCR2 and CXCM3 [i.e. CXCL 8/IL- 8, CXCL1/GRO- α and CXCL10/IP- 10), were absent in CNS tissue from no rmals and subjects with OND, but were present at high levels on hypertrophic (re active) astrocytes at the edge of active (but not silent) multiple sclerosis les ions. Astrocytes in vitro could be induced to express chemokines following stimu lation with pro- inflammatory cytokines. CXCL8 and CXCL1 production by human as trocytes at both the RNA and protein levels could be induced by interleukin (IL) - 1β , while CXCL10 was induced by both IL- 1β and interferon- γ . Since these cytokines are integral to inflammatory events occurring at the margins of active multiple sclerosis lesions, their upregulation in these regions may under lie the dynamics of chemokine expression observed herein. The simultaneous expression of differen t CXC chemokine receptors on oligodendrocytes, and their ligands on astrocytes a round multiple sclerosis lesions, may bespeak novel functional roles for these i mmune system molecules in the recruitment of oligodendrocytes and remyelination.展开更多
文摘Subsequent to demyelination in multiple sclerosis, myelin repair occurs but, as lesions age, the ability to remyelinate diminishes. Molecular pathways underl ying oligodendrocyte behaviour during CNS remyelination remain to be elucidated. In this study, we report for the first time constitutive expression of the CXC/ α chemokine receptors, CXCR1, CXCR2 and CXCR3, on oligodendrocytes in normal a dult human CNS tissue, the levels of which were upregulated in multiple sclerosi s and other neurological diseases (OND). In addition, both immature (A2B5+ /O4 + ) and more mature (CNPase+ ) human oligodendrocytes in vitro expressed the s ame three receptors. The respective ligands to CXCR1, CXCR2 and CXCM3 [i.e. CXCL 8/IL- 8, CXCL1/GRO- α and CXCL10/IP- 10), were absent in CNS tissue from no rmals and subjects with OND, but were present at high levels on hypertrophic (re active) astrocytes at the edge of active (but not silent) multiple sclerosis les ions. Astrocytes in vitro could be induced to express chemokines following stimu lation with pro- inflammatory cytokines. CXCL8 and CXCL1 production by human as trocytes at both the RNA and protein levels could be induced by interleukin (IL) - 1β , while CXCL10 was induced by both IL- 1β and interferon- γ . Since these cytokines are integral to inflammatory events occurring at the margins of active multiple sclerosis lesions, their upregulation in these regions may under lie the dynamics of chemokine expression observed herein. The simultaneous expression of differen t CXC chemokine receptors on oligodendrocytes, and their ligands on astrocytes a round multiple sclerosis lesions, may bespeak novel functional roles for these i mmune system molecules in the recruitment of oligodendrocytes and remyelination.
