Biomaterial Research Center, Cellinbio, Suwon 16681, Republic of Korea.
Department of Biology, Kongju National University, Kongju 32588, Republic of Korea.
J Microbiol Biotechnol. 2020 Dec 28;30(12):1810-1818. doi: 10.4014/jmb.2004.04062.
Inhibitor K562 (IK) protein was first isolated from the culture medium of K562 cells, a leukemia cell line, and is an inhibitory regulator of interferon-γ-induced major histocompatibility complex class II expression. Recently, exogenous truncated IK (tIK) protein showed potential as a therapeutic agent for inflammation-related diseases. In this study, we designed a novel putative anti-inflammatory peptide derived from tIK protein based on homology modeling of the human interleukin-10 (hIL-10) structure, and investigated whether the peptide exerted inhibitory effects against proinflammatory cytokines such as IL-17 and tumor necrosis factor-α (TNF-α). The peptide contains key residues involved in binding hIL-10 to the IL-10 receptor, and exerted strong inhibitory effects on IL- 17 (43.8%) and TNF-α (50.7%). In addition, we used circular dichroism spectroscopy to confirm that the peptide is usually present in a random coil configuration in aqueous solution. In terms of toxicity, the peptide was found to be biologically safe. The mechanisms by which the short peptide derived from human tIK protein exerts inhibitory effects against IL-17 and TNF-α should be explored further. We also evaluated the feasibility of using this novel peptide in skincare products.
抑素 K562(IK)蛋白最初从 K562 细胞(一种白血病细胞系)的培养基中分离出来,是干扰素-γ诱导主要组织相容性复合体 II 表达的抑制调节因子。最近,外源性截断的 IK(tIK)蛋白作为炎症相关疾病的治疗剂显示出潜力。在这项研究中,我们基于人白细胞介素 10(hIL-10)结构的同源建模设计了一种新型潜在的抗炎肽,来源于 tIK 蛋白,并研究了该肽是否对白细胞介素 17(IL-17)和肿瘤坏死因子-α(TNF-α)等促炎细胞因子发挥抑制作用。该肽包含与 hIL-10 结合到 IL-10 受体的关键残基,对 IL-17(43.8%)和 TNF-α(50.7%)表现出强烈的抑制作用。此外,我们使用圆二色性光谱证实该肽在水溶液中通常呈无规卷曲构象。就毒性而言,该肽被发现具有生物安全性。应该进一步探索源自人 tIK 蛋白的短肽对 IL-17 和 TNF-α 发挥抑制作用的机制。我们还评估了在护肤品中使用这种新型肽的可行性。