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Regulation of Proenkephalin A Messenger Ribonucleic Acid Levels in Normal B Lymphocytes: Specific Inhibition by Glucocorticoid Hormones and Superinduction by Cycloheximide^*

Department of Molecular Virology, Faculty of Medicine, The Hebrew University of Jerusalem Jerusalem, 91010
Department of Neurology, Neuroimmunology Research Unit, Hadassah University Hospital Jerusalem, 91120, Israel

Address all correspondence and requests for reprints to: Dr. Ovadia Haim, Department of Neurology, Hadassah University Hospital, P.O. Box 12000, Jerusalem, 91120, Israel.

Abstract

Proenkephalin A (PEA) encodes a group of small peptides known to function as neurotransmitters, neuromodulators, and neurohormones in the nervous and neuroendocrine systems. This gene has been shown to be expressed in lymphoid cells, supporting the concept of bidirectional communication between the immune system and the central nervous system. In the present study, we investigated the effect of steroids and the inhibition of protein and RNA syntheses on the regulation of PEA expression in normal rat B cells. The transient expression of PEA messenger (m) RNA levels occurring normally in B cells was markedly inhibited by the presence of either 50 nM prednisolone or dexamethasone, both of which are glucocorticoids; other steroids, such as testosterone or the steroidinactive metabolite androsterone, were ineffective. In the presence of cycloheximide, a protein synthesis inhibitor, PEA mRNA was superinduced by a factor of 15-fold. Sorting by flow cytometry of cycloheximide-treated cells followed by in situ hybridization analysis revealed that the expression of PEA mRNA was exclusively confined to a small fraction of B cells. These results indicate that the mechanisms regulating PEA gene expression in B cells differ from those previously described in cells of the neuroendocrine and the nervous systems.

Footnotes

^* This work was supported by grants from the Israeli National Council for Research and Development and the European Economic Community, the Israeli Ministry of Health, Chief Scientist Office.

Received January 17, 1991.

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