RESEARCH - Minocycline suppresses activation of NFAT1 in human CD4+ T cells

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J Biol Chem. 2011 Jan 31. [Epub ahead of print]

Minocycline suppresses activation of nuclear factor of activated T

cells 1 (NFAT1) in human CD4+ T cells.

Szeto GL, Pomerantz JL, Graham DR, Clements JE.

s Hopkins University School of Medicine, United States.

Abstract

Minocycline is a tetracycline family antibiotic that has

anti-inflammatory and immunomodulatory properties. These properties

have shown promise in the treatment of conditions such as rheumatoid

arthritis, Huntington's disease, and multiple sclerosis. Since

lymphocyte activation is involved in the pathogenesis of many of these

diseases, T cells are postulated to be a primary target in minocycline

therapy. Previous studies have demonstrated attenuation of CD4+ T cell

activation by minocycline, but a specific mechanism has not been

elucidated. In this study, we investigated the effect of minocycline

on the activity of three key transcription factors regulating CD4+ T

cell activation: nuclear factor êB (NF-ê, activator protein 1

(AP-1), and nuclear factor of activated T cells (NFAT). Our data

demonstrate that minocycline selectively impairs NFAT-mediated

transcriptional activation, a result of increased phosphorylation and

reduced nuclear translocation of the isoform NFAT1. Minocycline

increased the activity of the NFAT kinase GSK3 and decreased

intracellular Ca2+ flux, both of which facilitate NFAT1

phosphorylation. These findings provide a novel mechanism for

minocycline induced suppression of CD4+ T cell activation, and may

better inform the application of minocycline as an immunomodulatory

agent.

PMID: 21282105

http://www.ncbi.nlm.nih.gov/pubmed/21282105

Read the full article here:

http://www.jbc.org/content/early/2011/01/31/jbc.M110.210518.long

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