T lymphocytes conditioned with Interferon β induce membrane and soluble VCAM on human brain endothelial cells

Peter A. Calabresi, Alexandre Prat, Katherine Biernacki, Jessica Rollins, Jack P. Antel

Research output: Contribution to journalArticlepeer-review

Abstract

Vascular cell adhesion molecule (VCAM)-1 plays a critical role in mediating inflammatory cell adhesion and migration. Factors regulating the expression of membrane (m)VCAM and its cleaved counterpart soluble (s)VCAM are poorly understood. We previously demonstrated that serum sVCAM levels are increased in multiple sclerosis (MS) patients treated with interferon beta 1b (IFNβ1b), which correlated with a reduction in gadolinium enhancing lesions on magnetic resonance imaging. However, subsequent studies have shown that IFNβ does not directly induce VCAM expression on endothelial cells. We demonstrate here that co-culture with IFNβ-conditioned T cells induces mVCAM on human brain endothelial cells (HBEC). Further, rapid shedding of sVCAM occurs, which mirrors the response after in vivo IFNβ treatment. The VCAM induction is mediated partially through tumor necrosis factor (TNF)α and can be abrogated by sTNF receptor. VCAM could also be induced on astroglioma lines using IFNβ-conditioned T cells, which suggests the effect is not specific for HBEC. Kinetic studies demonstrated an increase in the sVCAM to mVCAM ratio over time, which may contribute to the ultimate therapeutic effect of IFNβ in patients. These data have important implications for understanding the events occurring at the blood brain barrier in vivo, and for determining the mechanism of action of IFNβ in MS.

Original languageEnglish (US)
Pages (from-to)161-167
Number of pages7
JournalJournal of Neuroimmunology
Volume115
Issue number1-2
DOIs
StatePublished - Apr 2 2001
Externally publishedYes

Keywords

  • Blood-brain barrier
  • Interferon β
  • Leukocyte
  • Multiple sclerosis
  • VCAM-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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