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α lipoic acid inhibits human T‐cell migration: Implications for multiple sclerosis
Author(s) -
Marracci Gail H.,
McKeon Gabriel P.,
Marquardt Whitney E.,
Winter Rolf W.,
Riscoe Michael K.,
Bourdette Dennis N.
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20255
Subject(s) - jurkat cells , fibronectin , microbiology and biotechnology , experimental autoimmune encephalomyelitis , cell adhesion , cell culture , cell migration , t cell , cell adhesion molecule , chemistry , cell , biology , immunology , biochemistry , multiple sclerosis , immune system , genetics
We have demonstrated previously the ability of the antioxidant 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 downmodulated 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. © 2004 Wiley‐Liss, Inc.