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

J Interferon Cytokine Res. 2002 Jun;22(6):631-40. doi: 10.1089/10799900260100114.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Astrocytes / drug effects*
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Brain / blood supply
  • Brain / cytology
  • Brain / metabolism*
  • Cells, Cultured
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / genetics*
  • Chemokines, CXC / metabolism*
  • Chemotaxis, Leukocyte / immunology
  • Culture Media, Conditioned
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Gene Expression Profiling
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / pharmacology*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Microcirculation
  • Multiple Sclerosis / etiology*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • RNA, Messenger / metabolism

Substances

  • Antibodies
  • CXCL11 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Chemokines, CXC
  • Culture Media, Conditioned
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Interleukin-10
  • Interferon-gamma