Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction.
Minocycline, a tetracycline with anti-inflammatory properties, has been reported to down-regulate the activity of microglia, whose activation occurs in inflammatory and degenerative diseases of the central nervous system, such as multiple sclerosis and Alzheimer's disease. In these disorders, a T cell component is also evident, and we have demonstrated previously that the interaction of activated T cells with microglia led to the substantial increase in tumor necrosis factor alpha (TNF-alpha) levels. Here, we report that minocycline decreases TNF-alpha levels produced in human T cell-microglia interaction. This effect is mediated by a direct action of minocycline on the activated T cells and on microglia, which resulted in the decreased ability of T cells to contact microglia. In correspondence, minocycline decreased the expression on T cells of the CD40 ligand (CD40L), a key molecule regulating the contact-mediated interaction of T cells with microglia. These results demonstrate that the mechanism of action of minocycline involves not only microglia but also T cells and their subsequent activation of microglia. The capacity of minocycline to down-regulate CD40L on T cells may provide a new means to target the CD40-CD40L pathway, which regulates several inflammatory processes.
Giuliani
Fabrizio
F
Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
Hader
Walter
W
Yong
V Wee
VW
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D008911:Minocycline / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D019013:CD40 Antigens; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D008911:Minocycline