α lipoic acid inhibits human T-cell migration: Implications for multiple sclerosis

Gail H. Marracci, Gabriel P. McKeon, Whitney E. Marquardt, Rolf W. Winter, Michael K. Riscoe, Dennis N. Bourdette

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

We have demonstrated previously the ability of the anti-oxidant α lipoic acid (ALA) to suppress and treat a model of multiple sclerosis (MS), relapsing experimental autoimmune encephalomyelitis (EAE). We describe the effects of ALA and its reduced form, dihydrolipoic acid (DHLA), on the transmigration of human Jurkat T cells across a fibronectin barrier in a transwell system. ALA and DHLA inhibited migration of Jurkat cells in a dose-dependent fashion by 16-75%. ALA and DHLA reduced matrix metalloproteinase-9 (MMP-9) activity by 18-90% in Jurkat cell supernatants. GM6001, a synthetic inhibitor of MMP, reduced Jurkat cell migration, but not as effectively as ALA and DHLA did. Both ALA and DHLA down-modulated the surface expression of the α4β1 integrin (very late activation-4 antigen; VLA-4), which binds fibronectin and its endothelial cell ligand vascular cell adhesion molecule-1 (VCAM-1). Moreover, ALA, but not DHLA, reduced MMP-9-specific mRNA and extracellular MMP-9 from Jurkat cells and their culture supernatants as detected by relative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. ALA and DHLA inhibited Jurkat cell migration and have different mechanisms for inhibiting MMP-9 activity. These data, coupled with its ability to treat relapsing EAE, suggest that ALA warrants investigation as a therapy for MS.

Original languageEnglish (US)
Pages (from-to)362-370
Number of pages9
JournalJournal of Neuroscience Research
Volume78
Issue number3
DOIs
StatePublished - Nov 1 2004

Keywords

  • Antioxidant
  • Matrix metalloproteinase-9
  • Transmigration

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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