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.

Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss

“…GV1001, a novel cell-penetrating peptide (16-amino-acid sequence) derived from human telomerase reverse transcriptase, has been implicated to have anticancer, antioxidant, anti-inflammatory, and antiapoptotic effects in kidney; it prevents myocardial ischemia-reperfusion injury; stimulates neural stem cell; and is active against various cancer types [7][8][9][10][11]. Moreover, our previous studies revealed that GV1001 significantly attenuated hearing threshold shift and cochlear outer hair cell (OHC) damage in kanamycin-induced ototoxicity mouse model [12,13].…”

In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components

“…Among these immune cells, the macrophage is one of the major effector cells governing inflammatory responses by producing various inflammatory mediators, including nitric oxide (NO), reactive oxygen/nitrogen species (ROS/RNS), prostaglandin E 2 (PGE 2 ), and different types of proinflammatory cytokines. The latter include tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 [under the control of the activator protein (AP)-1], nuclear factor kappa B (NF-κB), and interferon (IFN) regulatory factor 3 (IRF3) [2] , [3] , [4] , [5] , [6] , [7] . Although inflammation is a host defense mechanism to protect the body from invading pathogens, chronic inflammation, which is a prolonged state affecting tissue remodeling for several weeks to years, is regarded as a leading cause in the development of a variety of diseases, such as inflammatory/autoimmune diseases, neurodegenerative diseases, and cancers [8] , [9] , [10] .…”

Cinnamaldehyde Enhances Antimelanoma Activity through Covalently Binding ENO1 and Exhibits a Promoting Effect with Dacarbazine

“…ENO1 is known to induce inflammation through activation of the p38 MAPK and NF-κB signaling pathways [37]. Besides this, it is an effective inhibitor that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-κB activation following ENO1 stimulation [38]. It has also been observed that hypoxia significantly increases glucose uptake and that glucose transporter (GLUT) 1 and 3 expression are upregulated under hypoxia.…”