Synthetic (+)-terrein suppresses interleukin-6/soluble interleukin-6 receptor induced-secretion of vascular endothelial growth factor in human gingival fibroblasts

Hiroki Mandai, Kazuhiro Omori, Daisuke Yamamoto, Toki Tsumura, Kyouta Murota, Satoshi Yamamoto, Koichi Mitsudo, Soichiro Ibaragi, Akira Sasaki, Hiroshi Maeda, Shogo Takashiba, Seiji Suga

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Interleukin (IL)-6 is a proinflammatory cytokine that performs a wide variety of biological functions, including important roles in the progression of chronic inflammatory diseases such as periodontal disease. (+)-Terrein, a secondary bioactive fungal metabolite isolated from Aspergillus terreus, has various biological activities; however, its anti-inflammatory effects are still unknown. The purpose of this study was to examine the effect of synthetic (+)-terrein on IL-6 signaling and related protein production in human gingival fibroblasts. To our knowledge, this study is the first to report that synthetic (+)-terrein is not cytotoxic at concentrations less than 20 μM and suppresses IL-6/soluble IL-6 receptor (sIL-6R)-induced phosphorylation of signal transducer and activator of transcription-3, extracellular signal-regulated kinase 1/2, and c-jun N-terminal kinase 1/2 - signaling proteins that are downstream of IL-6 signaling. In addition, synthetic (+)-terrein suppresses IL-6/sIL-6R-induced vascular endothelial growth factor (VEGF) secretion in a concentration-dependent manner (p <0.01). These data suggest that synthetic (+)-terrein has potential anti-IL-6 signaling activity and suppresses VEGF-associated inflammatory disease progression.

Original languageEnglish
Pages (from-to)5338-5344
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number19
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • (+)-Terrein
  • Chronic inflammation
  • Human gingival fibroblast
  • IL-6
  • VEGF

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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