Bizzarri Cinzia, Beccari Andrea Rosario, Bertini Riccardo, Cavicchia Michela Rita, Giorgini Simona, Allegretti Marcello
Dompé Research Centre, Dompé pha.r.ma. s.p.a., Via Campo di Pile, 67100 L'Aquila, Italy.
Pharmacol Ther. 2006 Oct;112(1):139-49. doi: 10.1016/j.pharmthera.2006.04.002. Epub 2006 May 23.
ELR+ CXC chemokines, by direct interaction with their cell surface receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2), are believed to be crucially involved in the direct migration and activation of leukocytes. ELR+ CXC chemokines are supposed to play a key role in several inflammatory diseases and this makes ELR+ CXC chemokines and their receptors attractive therapeutic targets. The first aim of this review is to discuss the potential pathological role of ELR+ CXC chemokines in different pathologies, including ulcerative colitis (UC), ischaemia/reperfusion injury (RI), bronchiolitis obliterans syndrome (BOS) and tumor progression. Moreover, the most recently described inhibitors of ELR+ CXC chemokines and their therapeutic indications will be reviewed. Finally, the mode of action and the potential therapeutical use of reparixin, a new potent and selective inhibitor of CXCR1/2 activity, and its chemical derivatives are also discussed.
ELR+ CXC趋化因子通过与细胞表面受体CXC趋化因子受体1（CXCR1）和CXC趋化因子受体2（CXCR2）直接相互作用，被认为在白细胞的直接迁移和激活中起关键作用。ELR+ CXC趋化因子被认为在几种炎症性疾病中起关键作用，这使得ELR+ CXC趋化因子及其受体成为有吸引力的治疗靶点。本综述的首要目的是讨论ELR+ CXC趋化因子在不同病理状况下的潜在病理作用，包括溃疡性结肠炎（UC）、缺血/再灌注损伤（RI）、闭塞性细支气管炎综合征（BOS）和肿瘤进展。此外，还将综述最近描述的ELR+ CXC趋化因子抑制剂及其治疗适应症。最后，还讨论了一种新型强效且选择性的CXCR1/2活性抑制剂瑞帕霉素及其化学衍生物的作用模式和潜在治疗用途。
