title: The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production.
abstract: GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-κB activation following ENO1 stimulation.
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Jiyea
authors.initials: J
authors.lastname: Choi
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Yejin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Mirim
authors.initials: M
authors.lastname: Jang
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Jane
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwang
authors.affiliation: Department of Endodontics, Seoul National University School of Dentistry, Seoul 03080, Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Shon
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Medical Research Center, Seoul National University, Seoul 03080, Korea.; Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul National University, Seoul 03080, Korea.
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
keywords: ENO1; GV1001; Inflammation