The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production

  • Immune Netw. 2015 Dec;15(6):291-303. doi: 10.4110/in.2015.15.6.291.
Jiyea Choi  1 ,  Hyemin Kim  2 ,  Yejin Kim  1 ,  Mirim Jang  1 ,  Jane Jeon  1 ,  Young-Il Hwang  1 ,  Won Jun Shon  3 ,  Yeong Wook Song  4 ,  Jae Seung Kang  2 ,  Wang Jae Lee  1
Affiliations
  • 1. Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 2. 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.
  • 3. Department of Endodontics, Seoul National University School of Dentistry, Seoul 03080, Korea.
  • 4. 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.
PMID: 26770183 DOI: 10.4110/in.2015.15.6.291
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.

Keywords
ENO1; GV1001; Inflammation.
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