Investigation of the anti-inflammatory effect of GV1001, a peptide derived from human telomerase reverse transcriptase (hTERT) sequence

inflammation;GV1001;enolase1;rheumatoid arthritis;p38 MAPK;NF-κB;610

의과대학 의학과 ;

University:서울대학교 대학원

关键词: inflammation;    GV1001;    enolase1;    rheumatoid arthritis;    p38 MAPK;    NF-κB;    610;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/132794/1/000000067125.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

GV1001 is a peptide derived from human telomerase reverse transcriptase (hTERT) sequence, and has anti-cancer and anti-inflammatory effect. Enolase1 (ENO1) is a glycolytic enzyme and its stimulation induces to produce a large amount of pro-inflammatory cytokines from concanavalin (Con) A -activated peripheral blood mononuclear cells (PBMCs) and from ENO1 expressing monocytes and macrophages from rheumatoid arthritis (RA) patients. However, it is still unknown whether GV1001 could regulate the ENO1-mediated pro-inflammatory cytokines production. Therefore, I investigated whether GV1001 regulates ENO1-mediated pro-inflammatory cytokines production as an anti-inflammatory peptide. First, I found that GV1001 does not affect the expression of ENO1 on Con A-activated PBMCs and RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) from Con A-activated PBMCs. And it is down-regulated by the pre-treatment of GV1001. GV1001 also decreases the production of pro-inflammatory cytokines from ENO1 stimulated RA PBMCs. And then I examined what kinds of signaling molecules are involved in the down-regulation of ENO1-mediated pro-inflammatory cytokine production by GV1001. When ENO1 on the surface of Con A-activated PBMCs and RA PBMCs is stimulated, I found that p38 MAPK and NF-κB are activated. However, these are successfully suppressed by the pre-treatment of GV1001. Taken together, GV1001 might be a useful anti-inflammatory peptide via the down-regulation ofpro-inflammatory cytokine production and the suppression of the p38 MAPK and NF-κB activation by ENO1 stimulation.