Dual modulation of the T-cell receptor-activated signal transduction pathway by morphine in human T lymphocytes.

• Mizota, Toshiyuki

• Tsujikawa, Hiroshi

• Shoda, Takehiro

• Fukuda, Kazuhiko

Abstract

[Purpose]In this study, we aimed to investigate the effect of morphine on the activation of extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB), both of which play crucial roles in T-cell activation. [Methods]Human CD3+ T cells and Jurkat T cells were stimulated by anti-CD3 antibody or phorbol 12-myristate 13-acetate plus ionomycin with or without 24-h pretreatment with morphine. Activation of ERK was assessed by immunoblot analysis of phosphorylated ERK. Activation of the NF-κB signaling pathway was examined by analyzing nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation using immunoblotting, and interleukin-2 (IL-2) gene expression using quantitative real-time reverse-transcriptase polymerase chain reaction. [Results]Morphine pretreatment enhanced ERK phosphorylation, but inhibited IκBα phosphorylation and IL-2 gene expression in activated T cells. The effects of morphine on ERK phosphorylation and IL-2 gene expression were not antagonized by naloxone. We detected κ-opioid receptor transcript in T cells, but U50, 488, a κ-receptor-selective agonist, did not enhance ERK phosphorylation. [Conclusion]Morphine enhances ERK signaling, whereas it inhibits NF-κB signaling in activated human T cells. These effects of morphine are unlikely to be mediated by known opioid receptors.

Journal

• Journal of anesthesia

  Journal of anesthesia 27 (1), 80-87, 2013-02

  Springer Japan

Keywords

• Morphine
• Erk1/2
• Nuclear factor-κB
• Opioid-induced immunomodulation

Details

• CRID: 1050564285718073984
• NII Article ID: 10031165387
• NII Book ID: AA10852931
• ISSN: 09138668
• ISSN: 14388359
• DOI: 10.1007/s00540-012-1472-9
• HANDLE: 2433/172077
• Web Site: http://link.springer.com/content/pdf/10.1007/s00540-012-1472-9.pdf
• Web Site: http://link.springer.com/article/10.1007/s00540-012-1472-9/fulltext.html
• Web Site: http://link.springer.com/content/pdf/10.1007/s00540-012-1472-9
• Web Site: https://search.jamas.or.jp/link/ui/2014093281
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN