Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction

J Leukoc Biol. 2005 Jul;78(1):135-43. doi: 10.1189/jlb.0804477. Epub 2005 Apr 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology
  • Anti-Inflammatory Agents / pharmacology*
  • CD40 Antigens / immunology
  • CD40 Ligand / drug effects
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • Cell Communication / drug effects
  • Cell Communication / immunology*
  • Cell Line
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Humans
  • Immunity, Cellular / drug effects*
  • Immunity, Cellular / immunology
  • Immunosuppression
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Microglia / drug effects*
  • Microglia / immunology
  • Minocycline / pharmacology*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / drug effects*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • CD40 Antigens
  • Tumor Necrosis Factor-alpha
  • CD40 Ligand
  • Minocycline