Laboratory of Molecular Biology and Immunology, National Institute on Aging, Intramural Program, NIH, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
Int J Biol Sci. 2012;8(1):108-17. doi: 10.7150/ijbs.8.108. Epub 2011 Nov 26.
[D-Lys3]-Growth Hormone Releasing Peptide-6 (DLS) is widely utilized in vivo and in vitro as a selective ghrelin receptor (GHS-R) antagonist. Unexpectedly, we identified that DLS also has the ability to block CXCL12 binding and activity through CXCR4 on T cells and peripheral blood mononuclear cells (PBMCs). Moreover, as CXCR4 has been shown to act as a major co-receptor for HIV-1 entry into CD4 positive host cells, we have also found that DLS partially blocks CXCR4-mediated HIV-1 entry and propagation in activated human PBMCs. These data demonstrate that DLS is not the specific and selective antagonist as thought for GHS-R1a and appears to have additional effects on the CXCR4 chemokine receptor. Our findings also suggest that structural analogues that mimic DLS binding properties may also have properties of blocking HIV infectivity, CXCR4 dependent cancer cell migration and attenuating chemokine-mediated immune cell trafficking in inflammatory disorders.
[D-Lys3]-生长激素释放肽-6（DLS）在体内和体外广泛用作选择性胃饥饿素受体（GHS-R）拮抗剂。出乎意料的是，我们发现 DLS 还能够通过 T 细胞和外周血单核细胞（PBMC）上的 CXCR4 阻断 CXCL12 的结合和活性。此外，由于已经表明 CXCR4 作为 HIV-1 进入 CD4 阳性宿主细胞的主要共受体，我们还发现 DLS 部分阻断了 CXCR4 介导的人 PBMC 中 HIV-1 的进入和繁殖。这些数据表明，DLS 并不是 GHS-R1a 所认为的特异性和选择性拮抗剂，并且似乎对 CXCR4 趋化因子受体具有其他影响。我们的发现还表明，模拟 DLS 结合特性的结构类似物也可能具有阻断 HIV 感染性、CXCR4 依赖性癌细胞迁移以及减轻炎症性疾病中趋化因子介导的免疫细胞迁移的特性。
