• Mol Pain · Jan 2012

    JAK-STAT1/3-induced expression of signal sequence-encoding proopiomelanocortin mRNA in lymphocytes reduces inflammatory pain in rats.

    • Melanie Busch-Dienstfertig, Dominika Labuz, Theresa Wolfram, Nicole N Vogel, and Christoph Stein.
    • Department of Anesthesiology and Critical Care Medicine, Charité Campus Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. melanie.busch@charite.de
    • Mol Pain. 2012 Jan 1;8:83.

    BackgroundProopiomelanocortin (POMC)-derived beta-endorphin1-31 from immune cells can inhibit inflammatory pain. Here we investigated cytokine signaling pathways regulating POMC gene expression and beta-endorphin production in lymphocytes to augment such analgesic effects.ResultsInterleukin-4 dose-dependently elevated POMC mRNA expression in naïve lymph node-derived cells in vitro, as determined by real-time PCR. This effect was neutralized by janus kinase (JAK) inhibitors. Transfection of Signal Transducer and Activator of Transcription (STAT) 1/3 but not of STAT6 decoy oligonucleotides abolished interleukin-4 induced POMC gene expression. STAT3 was phosphorylated in in vitro interleukin-4 stimulated lymphocytes and in lymph nodes draining inflamed paws in vivo. Cellular beta-endorphin increased after combined stimulation with interleukin-4 and concanavalin A. Consistently, in vivo reduction of inflammatory pain by passively transferred T cells improved significantly when donor cells were pretreated with interleukin-4 plus concanavalin A. This effect was blocked by naloxone-methiodide.ConclusionInterleukin-4 can amplify endogenous opioid peptide expression mediated by JAK-STAT1/3 activation in mitogen-activated lymphocytes. Transfer of these cells leads to inhibition of inflammatory pain via activation of peripheral opioid receptors.

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