cAMP-response element binding protein (CREB) regulates cyclosporine-A- mediated down-regulation of cathepsin B and L synthesis

Kazuhiro Omori, Koji Naruishi, Tomoko Yamaguchi, Shun Ai Li, Mayumi Yamaguchi-Morimoto, Kaori Matsuura, Hideo Arai, Kohji Takei, Shogo Takashiba

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cyclosporin A (CsA) is an immunosuppressant with severe side effects including gingival overgrowth. We have previously reported that CsA impairs the activity of the lysosomal enzymes cathepsin B and L in human gingival fibroblasts (HGFs). Here, we have examined the effects of CsA on the DNA-binding activity of the cyclic AMP response element-binding protein (CREB) and cell viability, and the effects of CREB on cathepsin B and L synthesis and activity in HGFs. We have confirmed that CsA down-regulates cathepsin B and L synthesis. Further, CsA has no effect on cell viability and dramatically impairs CREB-DNA binding activity. Importantly, the synthesis of cathepsin B and L is down-regulated, and their activity is also significantly impaired in HGFs transfected with plasmid expressing dominant-negative CREB. These results suggest that CREB is essential for the CsA-mediated down-regulation of cathepsin B and L synthesis in HGFs.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalCell and Tissue Research
Volume330
Issue number1
DOIs
Publication statusPublished - Oct 2007

Keywords

  • CREB
  • Cathepsin
  • Cyclosporin A
  • Gingival fibroblasts
  • Gingival overgrowth
  • Human

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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