title: Synthetic (+)-terrein suppresses interleukin-6/soluble interleukin-6 receptor induced-secretion of vascular endothelial growth factor in human gingival fibroblasts.
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.
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. Electronic address: mandai@cc.okayama-u.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mandai
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Omori
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamamoto
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Toki
authors.initials: T
authors.lastname: Tsumura
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Kyouta
authors.initials: K
authors.lastname: Murota
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mitsudo
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ibaragi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Takashiba
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan; Research Center of New Functional Materials for Energy Production, Storage and Transport, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan; Japan Science and Technology Agency, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: suga@cc.okayama-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Suga
mesh_terms: D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D015394:Molecular Structure; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*; D000093242:Interleukin-6 Inhibitors
chemical_list: D003517:Cyclopentanes; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D042442:Vascular Endothelial Growth Factors; D000093242:Interleukin-6 Inhibitors; C439087:terrein
keywords: (+)-Terrein; Chronic inflammation; Human gingival fibroblast; IL-6; VEGF