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Mol Pain ; 8: 83, 2012 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-23146666

RESUMEN

BACKGROUND: Proopiomelanocortin (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. 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.


Asunto(s)
Inflamación/metabolismo , Janus Quinasa 3/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Dolor/metabolismo , Proopiomelanocortina/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Células Cultivadas , Concanavalina A/farmacología , Inflamación/tratamiento farmacológico , Interleucina-4/farmacología , Interleucina-4/uso terapéutico , Janus Quinasa 3/genética , Masculino , Naloxona/análogos & derivados , Naloxona/farmacología , Dolor/tratamiento farmacológico , Compuestos de Amonio Cuaternario/farmacología , ARN Mensajero , Ratas , Ratas Wistar , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT3/genética
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