CXC chemokines: the regulatory link between inflammation and angiogenesis

Chemokines are multifunctional mediators mainly responsible for leukocyte recruitment to inflamed tissues. Cytokines of the CXC family, however, also have a pivotal role in the control of inflammation and angiogenesis, as a result of the shared expression of their specific receptors by leukocytes and endothelial cells. Although the mechanisms of activity of angiogenic chemokines are known, the identification of those responsible for CXC chemokine-mediated angiostatic effects has been difficult. The recent discovery of a novel variant of CXCR3 (CXCR3-B) as a common receptor for all four angiostatic chemokines (CXCL4, CXCL9, CXCL10 and CXCL11) has enabled a better understanding of how CXC chemokines not only influence the sequential participation of inflammatory cells but also regulate, in a coordinate way, the inflammatory reaction leading to angiogenesis, tissue repair and new tissue generation. Dysregulation of this fine regulatory network can lead to abnormalities, such as chronic inflammation, dysplastic transformation and even tumor development and spreading. Thus, targeting of these chemokines or their receptors might provide a successful therapeutic approach in chronic inflammatory and neoplastic diseases.