Abstract

Increased levels of the anti-inflammatory peptide catestatin (CST), a cleavage product of the pro-hormone chromogranin A, correlates with less severe outcomes in hypertension, colitis and diabetes. However, it is unknown how CST reduces the infiltration of monocytes and macrophages in inflamed tissues. Here, we report that CST blocks leukocyte migration towards inflammatory chemokines. By in vitro and in vivo migration assays, we show that although CST itself is weakly chemotactic, it blocks migration of monocytes and granulocytes to inflammatory attracting factor CC-chemokine ligand 2 (CCL2) and macrophage inflammatory protein 2 (MIP-2). Moreover, it directs CX3CR1+ macrophages away from pancreatic islets. These findings support the emerging notion that CST is a key anti-inflammatory modulator.