Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes

Sabita Roy, Rebecca B. Chapin, Kelly J. Cain, Richard G. Charboneau, Sundaram Ramakrishnan, Roderick A. Barke

Research output: Contribution to journalArticle

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Abstract

Chronic treatment of mice with morphine affects the proliferation, differentiation, and function of immune cells. In the present study, we investigated the mechanism by which morphine inhibits phytohemagglutinin (PHA)/interleukln-1 (IL-1)-induced thymocyte proliferation. When compared to control cultures, morphinetreated thymocytes showed decreased steady-state levels of bioactive IL-2 and IL-2 mRNA. The reduced IL-2 concentration and reduced transcript levels correlated well with a decreased rate of synthesis of IL-2 mRNA as determined by nuclear runoff assays. Subsequent studies showed that morphine treatment affected transcriptional control elements of the IL-2 promoter by inhibiting the synthesis of a specific trans-activating nuclear factor, c-Fos. c-Fos mRNA levels measured by semiquantitative RT-PCR were significantly decreased in thymocytes following treatment with morphine and activation with PHA and IL-1. Under identical conditions, c-Jun mRNA levels were not altered. Electrophoretic mobility shift studies with the AP- 1 consensus oligonucleotide showed significantly decreased levels of AP-1- protein complex formation in nuclear extracts prepared from morphine-treated cells. These studies demonstrate for the first time that opioid alkaloids such as morphine can impair mitogen-lymphokine-activated thymocyte proliferation by interfering with transcriptional activation of the IL-2 gene.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCellular Immunology
Volume179
Issue number1
DOIs
StatePublished - Jul 10 1997
Externally publishedYes

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Thymocytes
Morphine
Transcriptional Activation
Interleukin-2
Messenger RNA
Transcription Factor AP-1
Phytohemagglutinins
Lymphokines
Mitogens
Alkaloids
Oligonucleotides
Opioid Analgesics
Polymerase Chain Reaction
Genes
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes. / Roy, Sabita; Chapin, Rebecca B.; Cain, Kelly J.; Charboneau, Richard G.; Ramakrishnan, Sundaram; Barke, Roderick A.

In: Cellular Immunology, Vol. 179, No. 1, 10.07.1997, p. 1-9.

Research output: Contribution to journalArticle

Roy, Sabita ; Chapin, Rebecca B. ; Cain, Kelly J. ; Charboneau, Richard G. ; Ramakrishnan, Sundaram ; Barke, Roderick A. / Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes. In: Cellular Immunology. 1997 ; Vol. 179, No. 1. pp. 1-9.
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