Abstract
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by blood-derived immune cells invading the CNS. This invasion could be determined by chemokines, and their role within the MS-affected brain is still poorly defined. We investigated the expression by RT-PCR and protein release by ELISA of the interferon-gamma (IFN-gamma)-inducible chemokines in human brain microvascular endothelial cells (HBMECs) and astrocytes. The monokine induced by IFN-gamma (Mig) behaves as a homing chemokine constitutively expressed in HBMECs and astrocytes, whereas the IFN-gamma-inducible 10-kDa protein (IP-10) and IFN-inducible T cell alpha-chemoattractant (I-TAC) are induced only after inflammatory stimuli. The biologic activity of IFN-gamma-inducible chemokines from an endothelial source was analyzed, and the transendothelial migration of activated lymphocytes was partly antagonized by specific antibodies, especially anti-Mig antibody. Our data highlight the capability of cells of the CNS to activate the chemoattractant machinery in a proinflammatory environment and in MS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies / pharmacology
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Astrocytes / drug effects*
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Astrocytes / immunology
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Astrocytes / metabolism
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Brain / blood supply
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Brain / cytology
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Brain / metabolism*
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Cells, Cultured
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Chemokine CXCL10
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Chemokine CXCL11
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Chemokine CXCL9
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Chemokines, CXC / biosynthesis
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Chemokines, CXC / genetics*
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Chemokines, CXC / metabolism*
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Chemotaxis, Leukocyte / immunology
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Culture Media, Conditioned
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism*
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Gene Expression Profiling
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Humans
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Intercellular Signaling Peptides and Proteins*
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Interferon-gamma / pharmacology*
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Interleukin-10 / biosynthesis
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Interleukin-10 / genetics*
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Interleukin-10 / metabolism
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / metabolism
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Microcirculation
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Multiple Sclerosis / etiology*
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Multiple Sclerosis / genetics
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Multiple Sclerosis / immunology
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RNA, Messenger / metabolism
Substances
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Antibodies
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CXCL11 protein, human
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CXCL9 protein, human
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Chemokine CXCL10
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Chemokine CXCL11
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Chemokine CXCL9
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Chemokines, CXC
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Culture Media, Conditioned
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Intercellular Signaling Peptides and Proteins
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RNA, Messenger
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Interleukin-10
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Interferon-gamma