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. General significance: Because it was shown that only the K 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 K opioid receptor, which leads to immune suppression by activation of P53-mediated signal transduction. (C) 2009 Elsevier B.V. All rights reserved.