Expression and modulation of IFN-gamma-inducible chemokines (IP-10, Mig, and I-TAC) in human brain endothelium and astrocytes: possible relevance for the immune invasion of the central nervous system and the pathogenesis of multiple sclerosis.
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.
Salmaggi
Andrea
A
Istituto Nazionale Neurologico "Carlo Besta," I-20133 Milan, Italy.
Gelati
Maurizio
M
Dufour
Anna
A
Corsini
Elena
E
Pagano
Stefano
S
Baccalini
Rossana
R
Ferrero
Elisabetta
E
Scabini
Silvia
S
Silei
Valerio
V
Ciusani
Emilio
E
De Rossi
Marco
M
D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008833:Microcirculation; D009103:Multiple Sclerosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism
D000906:Antibodies; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma