Identification of opioid-regulated genes in human lymphocytic cells by differential display: upregulation of Krüppel-like factor 7 by morphine.

Morphine was previously found to compromise the chemotactic mobility of leukocytic cells toward inflammatory sites as well as induce the expression of chemokine receptor CCR5, a coreceptor for HIV entry, on lymphocytes. Both effects increase the host's susceptibility for HIV infection. In this report, we used a reverse transcription-polymerase chain reaction-based differential display (RT-PCR DD), an RNA finger printing procedure, coupled with Northern slot blot hybridization, in identifying gene or genes regulated by morphine in human lymphocytic cells. Ten positive gene segments, including two morphine downregulated genes and eight morphine upregulated genes, were identified. Analysis of the DNA sequences of these gene segments showed high homologies to known DNA and protein sequences on databases, of which two apoptosis/cell growth-related genes (PNAS-133 and Krüppel-like factor 7) were revealed. PNAS-133 gene was downregulated by morphine whereas the Krüppel-like factor 7 (KLF7), a zinc finger transcription factor, was upregulated by morphine. The upregulation of KLF7 by morphine was further studied and found to be at both the transcriptional and the translational levels in a naloxone-reversible manner. Cell growth was promoted by morphine up to day 4 (72 h) post treatment. These findings suggest a unique role for morphine in regulating cell proliferation and differentiation of immune cells.