The anti-inflammatory peptide Catestatin blocks chemotaxis

Abstract

Increased levels of the anti-inflammatory peptide Catestatin (CST), a cleavage product of the pro-hormone chromogranin A, correlate with less severe outcomes in hypertension, colitis, and diabetes. However, it is unknown how CST reduces the infiltration of monocytes and macrophages (Mϕs) in inflamed tissues. Here, it is reported that CST blocks leukocyte migration toward inflammatory chemokines. By in vitro and in vivo migration assays, it is shown that although CST itself is chemotactic, it blocks migration of monocytes and neutrophils to inflammatory attracting factor CC-chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 2 (CXCL2). Moreover, it directs CX 3 CR1 + Mϕs away from pancreatic islets. These findings suggest that the anti-inflammatory actions of CST are partly caused by its regulation of chemotaxis.

Reduction in CgA-Derived CST Protein Level in HTR-8/SVneo and BeWo Trophoblastic Cell Lines Caused by the Preeclamptic Environment

“…It is characterized, among others, by its pro-angiogenic and anti-inflammatory effects, hypotensive way of action, and its role in the defense against oxidative stress-induced apoptosis [ 29 , 30 , 31 ]. Although the exact mechanism by which CST reduces infiltration by monocytes and macrophages remains unknown, it may be connected with its regulation of chemotaxis [ 32 ]. CST has also been found to demonstrate pro-angiogenic potential in vitro and in vivo.…”

Role of Catestatin in the Cardiovascular System and Metabolic Disorders

“…Further, after vascular injury, Cts increased the expression of Mrc1 , a gene encoding an anti-inflammatory peptide, and prevented macrophage-driven atherosclerosis ( 75 ). Presumably, anti-inflammatory actions of Cts partly depend on the regulation of chemotaxis ( 102 ). In vitro and in vivo (rodent models), Cts counteracted chemoattraction of monocytes and neutrophils by inflammatory chemokines ( 102 ), likely contributing to reduced immune infiltration in the heart ( 21 , 75 ).…”

“…Presumably, anti-inflammatory actions of Cts partly depend on the regulation of chemotaxis ( 102 ). In vitro and in vivo (rodent models), Cts counteracted chemoattraction of monocytes and neutrophils by inflammatory chemokines ( 102 ), likely contributing to reduced immune infiltration in the heart ( 21 , 75 ). Regulation of chemotaxis by Cts is complex and naturally occurring Cts variants differ in their chemotactic properties ( 103 , 104 ), which may influence the propensity for CVD.…”

“…To sum up, it is increasingly clear that Cts is vital for maintaining metabolic homeostasis, which is partly achieved by affecting the immune system. Based on in vitro and in vivo experimental studies, Cts may inhibit inflammatory response and leukocyte-endothelial cell interactions ( 19 , 21 , 75 , 102 , 103 ), prevent macrophage-driven atherosclerosis ( 19 , 75 ), regulate monocyte migration ( 103 ), and cytokine production and release ( 102 – 104 ). As a novel regulator of metabolism, in rodents, Cts was shown to help in achieving insulin sensitivity, overcoming endoplasmic reticulum stress ( 106 ), reducing adipose tissue by increasing lipolysis, enhancing oxidation of fatty acids, and their assimilation into lipids ( 22 ).…”

The immunomodulatory functions of chromogranin A-derived peptide pancreastatin

“…1). These peptides have a broad spectrum of regulatory behavior, which influences glucose [32][33][34][35][36] and calcium-homeostasis [37], and the cardiovascular [38][39][40][41] and the immune systems [34,36,42,43]. Moreover, this list is not complete and other cleavage products, regulated by proteolysis, display different biological activities.…”