Chemokines are a family of low molecular weight
proteins with an essential role in leukocyte trafficking during both homeostasis and
inflammation. The CC class of
chemokines consists of at least 28 members (CCL1-28) that signal through 10 known
chemokine receptors (CCR1-10).
CC chemokine receptors are expressed predominantly by T cells and monocyte-macrophages, cell types associated predominantly with chronic
inflammation occurring over weeks or years. Chronic inflammatory diseases including
rheumatoid arthritis,
atherosclerosis, and
metabolic syndrome are characterized by continued leukocyte infiltration into the inflammatory site, driven in large part by excessive
chemokine production. Over years or decades, persistent
inflammation may lead to loss of tissue architecture and function, causing severe disability or, in the case of
atherosclerosis, fatal outcomes such as
myocardial infarction or
stroke. Despite the existence of several clinical strategies for targeting chronic
inflammation, these diseases remain significant causes of morbidity and mortality globally, with a concomitant economic impact. Thus, the development of novel therapeutic agents for the treatment of chronic inflammatory disease continues to be a priority. In this review we introduce
CC chemokine receptors as critical mediators of chronic inflammatory responses and explore their potential role as pharmacological targets. We discuss functions of individual
CC chemokine receptors based on in vitro pharmacological data as well as transgenic animal studies. Focusing on three key forms of chronic
inflammation--
rheumatoid arthritis,
atherosclerosis, and
metabolic syndrome--we describe the pathologic function of
CC chemokine receptors and their possible relevance as therapeutic targets.