Anti-CD3 activation of human CD4+ T cells increases expression of the intracellular β-endorphin endopeptidase (IDE/γ-EpGE)

Boppana Sarada, Dwain L Thiele, Tuyet Dang, Jong Lee, Afshin Safavia, Louis B. Hersh, Gene L. Cottam

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

In this study, increased expression of an endopeptidase hydrolyzing β- endorphin (β-Ep) to γ-endorphin (γ-Ep, β-Ep1-17) was observed upon immobilized anti-CD3 stimulated activation of human peripheral blood CD4+ T cells (hCD4+ T cells). Although freshly isolated hCD4+ T cells are devoid of significant β-Ep endopeptidase activity (< 0.1 nmol h-1 106 cells- 1), activation of these cells with immobilized anti-CD3 results in a time dependent appearance of β-Ep endopeptidase activity which reaches a maximal value of 17.4 ± 0.48 nmol h-1 106 cells-1 after 48 h of culture. Significant up-regulation of both mRNA encoding IDE/γ-EpGE and immunoreactive protein are observed in anti-CD3 stimulated hCD4+ T cells, indicating transcription and translation of IDE/γ-EpGE may be elevated. No significant hydrolysis of exogenous β-Ep is observed with intact hCD4+ T cells whether quiescent or activated or from preparations of hCD4+ T cell membranes. Therefore, this activity appears to be intracellular. Immunoreactive IDE/γ-EpGE is detected inside activated hCD4+ T cells. Analysis of metabolites generated upon hydrolysis of β-Ep with lysed activated hCD4+ T cell preparations identified the presence of: β-Ep1-18, β-Ep2-18, β-Ep1-17, β-Ep2-17, β-Ep18-31, β-Ep19-31, β-Ep1-13, β-Ep2- 13, β-Ep18-26, and β-Ep20-31 as major metabolites and the majority of these are consistent with β-Ep hydrolytic activity attributable to IDE/γ-EpGE.

Original languageEnglish (US)
Pages (from-to)59-68
Number of pages10
JournalJournal of Neuroimmunology
Volume85
Issue number1
DOIs
StatePublished - May 1 1998

Keywords

  • HCD4 T cells
  • Insulin degrading enzyme (IDE)
  • β-Endorphin
  • γ-Endorphin generating enzyme

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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