WKYMVm

WKYMVm is a potent N-formyl peptide receptor (FPR1) and FPRL1/2 agonist, and also activate phosphoinositide hydrolysis in undifferentiated HL-60 cells.^[1]

In vitro efficacy test indicated that treatment with 0.01, 0.1, 1 and 10 μmol/L WKYMVm for 24 hours or 48 hours obviouly suppressed RANKL‐induced mature osteoclasts.^[3] In vitro, treatment with 10 μM WKYMVm to stimulate FPR2 can induce p47phox phosphorylation in IMR90 fibroblasts and in human lung cancer cells, which is considered the key event for NADPH oxidase-dependent superoxide generation. Moreover, 10 μM WKYMVm to stimulate also induced NADPH oxidase-dependent superoxide generation with maximal production occurring at 2 min.^[6]

In vivo experiment it shown that treatment with 2.5- and 5 mg/kg/d daily over four days intraperitoneally in ALI mice decreased the levels of proinflammatory cytokines TNF-α, IL-6, and IL-1β, while it increased the MPO and NO release by differentiated HL-60 neutrophil-like cells.^[2].

Intramuscular injection of 10?5 mol/l WKYMVm improves blood perfusion and provides protection from tissue damage in the ischemic hind limb.^[4] In vivo, treatment with 8 mg/kg WKYMVm subcutaneously (at 0, 12, 24, 36, 48 and 60h) effectively attenuated the DSS-induced increase in the bleeding score and the stool score and protects dextran sodium sulfate (DSS)-induced experimental ulcerative colitis.^[5] In addition, administration of 4 mg/kg WKYMVm, to septic mice strongly increased neutrophil number through augmented emergency granulopoiesis^[7].

References:
[1]. Christophe T, et al. The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2. J Biol Chem. 2001 Jun 15;276(24):21585-93.
[2]. Lee H, et al. WKYMVm ameliorates acute lung injury via neutrophil antimicrobial peptide derived STAT1/IRF1 pathway. Biochem Biophys Res Commun. 2020 Dec 10;533(3):313-318.
[3]. Hu J, et al. The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF-κB and CD9/gp130/STAT3 signalling pathway. J Cell Mol Med. 2020 Jan;24(2):1893-1905.
[4]. Heo SC, et al. WKYMVm-induced activation of formyl peptide receptor 2 stimulates ischemic neovasculogenesis by promoting homing of endothelial colony-forming cells. Stem Cells. 2014 Mar;32(3):779-90.
[5]. Kim SD, et al. The immune-stimulating peptide WKYMVm has therapeutic effects against ulcerative colitis. Exp Mol Med. 2013 Sep 13;45(9):e40.
[6]. Cattaneo F, et al. WKYMVm-induced cross-talk between FPR2 and HGF receptor in human prostate epithelial cell line PNT1A. FEBS Lett. 2013 May 21;587(10):1536-42.
[7]. Kim HS, et al. Activation of formyl peptide receptor 2 by WKYMVm enhances emergency granulopoiesis through phospholipase C activity. BMB Rep. 2018 Aug;51(8):418-423.

WKYMVm 是一种有效的 N-甲酰肽受体 (FPR1) 和 FPRL1/2 激动剂，还可以激活未分化 HL-60 细胞中的磷酸肌醇水解。^[1]

体外药效试验表明，0.01、0.1、1和10μmol/L WKYMVm处理24小时或48小时明显抑制RANKL诱导的成熟破骨细胞。^[3]用 10 μM WKYMVm 刺激 FPR2 可诱导 IMR90 成纤维细胞和人肺癌细胞中的 p47phox 磷酸化，这被认为是 NADPH 氧化酶依赖性超氧化物生成的关键事件。此外，10 μM WKYMVm 刺激还诱导 NADPH 氧化酶依赖性超氧化物的产生，最大产生发生在 2 分钟。^[6]

体内实验表明，每天 2.5 和 5 mg/kg/d 腹膜内注射 ALI 小鼠 4 天可降低促炎细胞因子 TNF-α、IL-6 和 IL-1β 的水平，同时增加分化的 HL-60 中性粒细胞样细胞释放 MPO 和 NO。^[2].

肌内注射 10-5 mol/l WKYMVm 可改善血液灌注并保护缺血后肢免受组织损伤。^[4] 在体内，皮下注射 8 mg/kg WKYMVm (在 0、12、24、36、48 和 60h 时）有效减弱了 DSS 引起的出血评分和粪便评分的增加，并保护了葡聚糖硫酸钠 (DSS) 引起的实验性溃疡性结肠炎。^{[5]< /sup> 此外，对败血症小鼠施用 4 mg/kg WKYMVm 通过增强紧急粒细胞生成显着增加中性粒细胞数量[7]。}