Morphine induces DNA damage and P53 activation in CD3+ T cells.
BACKGROUND
Morphine has been shown to affect the function of immune system, but the precise mechanism remains to be elucidated. The present study was aimed to clarify the mechanism for the morphine-induced immune suppression by analyzing the direct effect of morphine on human CD3+ T cells.


METHODS
To identify genes up-regulated by action of morphine on the opioid receptor expressed in CD3+ T cells, PCR-select cDNA subtraction was performed by the use of total RNA from human CD3+ T cells treated with morphine in the presence and absence of naloxone.


RESULTS
We show that p53 and damage-specific DNA binding protein 2 (ddb2) genes are up-regulated by morphine in a naloxone-sensitive manner. Furthermore, the results indicate that DNA damage, quantified by apurinic-apyrimidinic site counting assay and phosphorylation of Ser-15 in P53 protein, is induced in CD3+ T cells by morphine in a naloxone-sensitive manner.


CONCLUSIONS
Because it was shown that only the kappa opioid receptor gene is expressed in CD3+ T cells in the opioid receptor family, the present study suggests that morphine induces DNA damage through the action on the kappa opioid receptor, which leads to immune suppression by activation of P53-mediated signal transduction.
Tsujikawa
Hiroshi
H
Department of Critical Care Medicine, Kyoto University Hospital, Kyoto 606-8507, Japan. klotho@kuhp.kyoto-u.ac.jp
Shoda
Takehiro
T
Mizota
Toshiyuki
T
Fukuda
Kazuhiko
K
D000328:Adult; D017252:CD3 Complex / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010768:Phosphoserine / Q000378:metabolism; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D017252:CD3 Complex; D050759:Cyclin-Dependent Kinase Inhibitor p21; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D011957:Receptors, Opioid; D016159:Tumor Suppressor Protein p53; D010768:Phosphoserine; D009270:Naloxone; D009020:Morphine