Abstract：
Inflammatory chemokines are often elevated in disease settings, where the largest group of CC-chemokines are the macrophage inflammatory proteins (MIP), which are promiscuous for the receptors CCR1 and CCR5. MIP chemokines, such as CCL3 and CCL5 are processed at the N terminus, which influences signaling in a highly diverse manner. Here, we investigate the signaling capacity of peptides corresponding to truncated N termini. These 3-10-residue peptides displayed weak potency but, surprisingly, retained their signaling on CCR1. In contrast, none of the peptides generated a signal on CCR5, but a CCL3-derived tetrapeptide was a positive modulator boosting the signal of several chemokine variants on CCR5. In conclusion, chemokine N termini can be mimicked to produce small CCR1-selective agonists, as well as CCR5-selective modulators.
摘要：
炎症趋化因子通常在疾病环境中升高，其中最大的CC趋化因子是巨噬细胞炎性蛋白（MIP），它们对受体CCR1和CCR5是混杂的。MIP趋化因子,如CCL3和CCL5在N端加工，以高度多样化的方式影响信号传导。这里,我们研究了与截短的N末端相对应的肽的信号传导能力。这些3至10个残基的肽显示弱效力，但是，令人惊讶的是,将其信令保留在CCR1上。相比之下,没有一种肽在CCR5上产生信号,但是CCL3衍生的四肽是增强CCR5上几种趋化因子变体的信号的正调节剂。总之,趋化因子N端可以模拟产生小的CCR1选择性激动剂，以及CCR5选择性调节剂。
