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Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis
Gail H Marracci1, Gabriel P McKeon, Whitney E Marquardt
1Portland Veterans Affairs Medical Center, Portland, Oregon, USA.
Journal of Neuroscience Research
|September 25, 2004
Summary
Alpha lipoic acid (ALA) and dihydrolipoic acid (DHLA) inhibit T-cell migration and reduce matrix metalloproteinase-9 (MMP-9) activity. These findings suggest ALA
Area of Science:
- Neuroimmunology
- Cellular and Molecular Biology
- Pharmacology
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system.
- Relapsing experimental autoimmune encephalomyelitis (EAE) is a common animal model for MS.
- Alpha-lipoic acid (ALA) has shown potential in treating EAE.
Purpose of the Study:
- To investigate the effects of ALA and its reduced form, dihydrolipoic acid (DHLA), on T-cell transmigration.
- To elucidate the mechanisms by which ALA and DHLA affect T-cell migration and matrix metalloproteinase-9 (MMP-9) activity.
Main Methods:
- Utilized a transwell system to assess human Jurkat T-cell migration across a fibronectin barrier.
- Measured MMP-9 activity in cell supernatants using enzyme-linked immunosorbent assay (ELISA).
- Assessed surface expression of alpha4beta1 integrin (VLA-4) and MMP-9 mRNA levels via RT-PCR.
Main Results:
- Both ALA and DHLA significantly inhibited Jurkat T-cell migration in a dose-dependent manner.
- ALA and DHLA reduced MMP-9 activity and downmodulated VLA-4 surface expression.
- ALA, but not DHLA, reduced MMP-9 mRNA and extracellular MMP-9 levels.
Conclusions:
- ALA and DHLA effectively inhibit T-cell migration through distinct mechanisms, including MMP-9 modulation and VLA-4 downmodulation.
- The findings support further investigation of ALA as a potential therapeutic agent for MS.