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

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10 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

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

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Interleukin-6 Receptors
Fibroblasts
Vascular Endothelial Growth Factor A
Interleukin-6
Mitogen-Activated Protein Kinase 9
Mitogen-Activated Protein Kinase 8
STAT3 Transcription Factor
Phosphorylation
Mitogen-Activated Protein Kinase 3
Aspergillus
Mitogen-Activated Protein Kinase 1
Periodontal Diseases
Metabolites
Bioactivity
Proteins
Chronic Disease
Anti-Inflammatory Agents
terrein
human VEGFA protein
Cytokines

Keywords

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

ASJC Scopus subject areas

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

Cite this

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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",
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author = "Hiroki Mandai and Kazuhiro Omori and Daisuke Yamamoto and Toki Tsumura and Kyouta Murota and Satoshi Yamamoto and Koichi Mitsudo and Soichiro Ibaragi and Akira Sasaki and Hiroshi Maeda and Shogo Takashiba and Seiji Suga",
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T1 - Synthetic (+)-terrein suppresses interleukin-6/soluble interleukin-6 receptor induced-secretion of vascular endothelial growth factor in human gingival fibroblasts

AU - Mandai, Hiroki

AU - Omori, Kazuhiro

AU - Yamamoto, Daisuke

AU - Tsumura, Toki

AU - Murota, Kyouta

AU - Yamamoto, Satoshi

AU - Mitsudo, Koichi

AU - Ibaragi, Soichiro

AU - Sasaki, Akira

AU - Maeda, Hiroshi

AU - Takashiba, Shogo

AU - Suga, Seiji

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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

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KW - Chronic inflammation

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KW - VEGF

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