The regulation and importance of monocyte chemoattractant protein-1

Abstract

Purpose of review: Monocyte chemoattractant protein (MCP)-1, a chemokine regulating monocyte chemotaxis and T-lymphocyte differentiation by binding to the CC chemokine receptor 2 (CCR2), plays a crucial role in the pathogenesis of inflammatory diseases, atherosclerosis and cancer. This review summarizes the current knowledge on the regulation and importance of the MCP-1/CCR2 axis, focusing on the therapeutic potential of its inhibition.

Recent findings: Differential modulation of MCP-1 and CCR2 lead to downstream activation pathways, pathogenetic to differing disease conditions characterized by dysregulated monocyte/macrophage tissue recruitment. Pharmacological targeting of the MCP-1/CCR2 axis has led to selective MCP-1/CCR2 antagonists that have now entered phase I/II clinical trials for the treatment of inflammatory diseases, atherosclerosis and cancer. The pleiotropic nonselective MCP-1/CCR2 inhibition by current pharmacological agents is thought to contribute to their anti-inflammatory and antiatherosclerotic effects that is also seen for nutraceutical compounds such as curcumin.

Summary: MCP-1 has a critical role in regulating chemotaxis both in health and disease, with increasing interest in its pharmacological inhibition. However, the therapeutic efficacy and safety of targeting the MCP-1/CCR2 axis is still in evolution.