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

Molecular Pain

Christoph Stein¹  Nicole N Vogel¹  Theresa Wolfram²  Dominika Labuz¹  Melanie Busch-Dienstfertig¹ 

[1] Department of Anesthesiology and Critical Care Medicine, Charité Campus Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200, Berlin, Germany;current address: MorphoSys AG, Lena-Christ-Str. 48, 82152, Martinsried/Planegg, Germany

关键词: Cytokine signaling.;    Neuro-immune interactions;    Immune cells;    Opioid peptides;    Inflammation;    Pain;   

Others  :  863323
DOI  :  10.1186/1744-8069-8-83

 received in 2012-06-25, accepted in 2012-11-06,  发布年份 2012

【 摘 要 】

Background

Proopiomelanocortin (POMC)-derived beta-endorphin_1-31 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.

Results

Interleukin-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.

Conclusion

Interleukin-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.

【 授权许可】

   
2012 Busch-Dienstfertig et al.; licensee BioMed Central Ltd.

【 图 表 】

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