The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production.
The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production.
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DOI：
10.4110/in.2015.15.6.291
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发表时间：
2015-12
期刊：
影响因子：
6
通讯作者：
Lee WJ
中科院分区：
文献类型：
--
作者：
Choi J;Kim H;Kim Y;Jang M;Jeon J;Hwang YI;Shon WJ;Song YW;Kang JS;Lee WJ
GV 1001是一种来源于人端粒酶逆转录酶（hTERT）序列的肽，据报道具有抗癌和抗炎作用。烯醇化酶1（ENO 1）是一种糖酵解酶，该酶的刺激可诱导健康受试者伴刀豆球蛋白A（Con A）激活的外周血单核细胞（PBMC）和表达ENO 1的单核细胞以及类风湿性关节炎（RA）患者巨噬细胞产生高水平的促炎细胞因子。因此，本研究调查是否GV 1001下调ENO 1诱导的促炎细胞因子作为抗炎肽。结果表明，GV 1001不影响Con A激活的PBMC和RA PBMC中ENO 1的表达。然而，ENO 1刺激增加了促炎细胞因子如肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL-6的产生，并且这些细胞因子在GV 1001预处理后下调。此外，当Con A激活的PBMC和RA PBMC表面的ENO 1被刺激时，p38丝裂原活化蛋白激酶（MAPK）和核因子（NF）-κB被激活，并且它们被GV 1001预处理成功地抑制。这些结果表明，GV 1001可能是一种有效的抗炎肽，其通过抑制ENO 1刺激后p38 MAPK和NF-κB活化来下调促炎细胞因子的产生。
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.