All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-δ

Akira Uruno, Naoya Noguchi, Ken Matsuda, Koji Nata, Takeo Yoshikawa, Youichiro Chikamatsu, Hiroyuki Kagechika, Hideo Harigae, Sadayoshi Ito, Hiroshi Okamoto, Akira Sugawara

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

ATRA and a synthetic RAR agonist tamibarotene (Am80) induce granulocytic differentiation of human acute leukemia HL-60 cells and have been used in antineoplastic therapy. ATRA induces CD38 antigen during HL-60 cell differentiation, which interacts with CD31 antigen on the vascular EC surface and may induce disadvantages in the therapy. We here examined the mechanisms of the ATRA-mediated CD38 induction and compared the difference between ATRA- and tamibarotene- mediated induction. Tamibarotene-induced HL-60 cell adhesion to ECs was 38% lower than ATRA, and NB4 cell adhesion to ECs by tamibarotene was equivalent to ATRA, which induced CD38 gene transcription biphasically in HL-60 cells, the early-phase induction via DRRARE containing intron 1, and the delayed-phase induction via RARE lacking the 5′-flanking region. In contrast to ATRA, tamibarotene induced only the early-phase induction, resulting in its lower CD38 induction than ATRA. A PKCδ inhibitor, rottlerin, and siRNA-mediated PKCδ knockdown suppressed the ATRA-induced CD38 promoter activity of the 5′-flanking region, whereas a RAR antagonist, LE540, or RAR knockdown did not affect it. Cycloheximide and rottlerin suppressed the delayedphase induction of CD38 expression by ATRA but did not affect the early-phase induction. Moreover, ATRA, but not tamibarotene, induced PKCδ expression without affecting its mRNA stability. The diminished effect of tamibarotene on CD38-mediated HL-60 cell adhesion to ECs compared with ATRA is likely a result of the lack of its delayed- phase induction of CD38 expression, which may be advantageous in antineoplastic therapy.

Original languageEnglish
Pages (from-to)235-247
Number of pages13
JournalJournal of Leukocyte Biology
Volume90
Issue number2
DOIs
Publication statusPublished - 2011 Aug

Keywords

  • Adhesion
  • Endothelial cells
  • Retinoic acid receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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