title: Dual modulation of the T-cell receptor-activated signal transduction pathway by morphine in human T lymphocytes.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto, 606-8507, Japan. mizota@kuhp.kyoto-u.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mizota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsujikawa
authors.forename: Takehiro
authors.initials: T
authors.lastname: Shoda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D015153:Blotting, Western; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D020672:I-kappa B Proteins; D016328:NF-kappa B; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D011957:Receptors, Opioid; D012313:RNA; D009020:Morphine