TY - JOUR
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
N1 - Funding Information:
The authors gratefully thank Division of Instrumental Analysis, Department of Instrumental Analysis & Cryogenics, Advanced Science Research Center, Okayama University for the NMR, high-resolution mass spectrometry measurements (FAB), and X-ray single crystal structural analyses. Financial support was partially provided by Wesco Scientific Promotion (to H.M.), the Japan Society for the Promotion of Science in the form of Grants-in-Aid for Scientific Research ( 22792083 ; to K.O.), 2010 Okayama University Grants Fostering Young Researcher Groups for Interdisciplinary Sciences (to H.M., K.O., and S.I.) and Kobayashi Magobe Memorial Medical Foundation (to K.O.).
Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
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 <0.01). These data suggest that synthetic (+)-terrein has potential anti-IL-6 signaling activity and suppresses VEGF-associated inflammatory disease progression.
AB - 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.
KW - (+)-Terrein
KW - Chronic inflammation
KW - Human gingival fibroblast
KW - IL-6
KW - VEGF
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U2 - 10.1016/j.bmc.2014.07.047
DO - 10.1016/j.bmc.2014.07.047
M3 - Article
C2 - 25151086
AN - SCOPUS:84907563473
VL - 22
SP - 5338
EP - 5344
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 19
ER -