Catestatin as a Target for Treatment of Inflammatory Diseases.

Elke M Muntjewerff,Gina Dunkel,Mara J T Nicolasen,Sushil K Mahata,Geert Van Den Bogaart

doi:10.3389/fimmu.2018.02199

Abstract

It is increasingly clear that inflammatory diseases and cancers are influenced by cleavage products of the pro-hormone chromogranin A (CgA), such as the 21-amino acids long catestatin (CST). The goal of this review is to provide an overview of the anti-inflammatory effects of CST and its mechanism of action. We discuss evidence proving that CST and its precursor CgA are crucial for maintaining metabolic and immune homeostasis. CST could reduce inflammation in various mouse models for diabetes, colitis and atherosclerosis. In these mouse models, CST treatment resulted in less infiltration of immune cells in affected tissues, although in vitro monocyte migration was increased by CST. Both in vivo and in vitro, CST can shift macrophage differentiation from a pro- to an anti-inflammatory phenotype. Thus, the concept is emerging that CST plays a role in tissue homeostasis by regulating immune cell infiltration and macrophage differentiation. These findings warrant studying the effects of CST in humans and make it an interesting therapeutic target for treatment and/or diagnosis of various metabolic and immune diseases.

Highlights

Inflammation-based diseases, such as chronic inflammation (Type 2 diabetes Mellitus (T2DM) and colitis), auto-immune diseases (rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)), hypertension, tumor metastasis and development of severe cancers [1,2,3] are major health problems
CST injections in CgAKO mice resulted in decreased triglyceride levels in the plasma and reduced fat depot sizes by ∼25% [63]. These findings indicate that CST promotes lipid flux from adipose tissue to the liver for beta oxidation, which might explain the frequently observed weight gain in patients with inflammatory diseases, as these patients have lower plasma levels of CST [75, 95, 98]
In the Diet-induced obese (DIO) mouse model, intra-peritoneal injections with CST reduced plasma levels of pro-inflammatory cytokines and chemokines (TNF-α, INF-γ, and CC-chemokine ligand 2 (CCL2)) [75]. These findings indicate that CST shifts macrophage differentiation from a pro- to a more anti-inflammatory phenotype

Summary

Introduction

Inflammation-based diseases, such as chronic inflammation (Type 2 diabetes Mellitus (T2DM) and colitis), auto-immune diseases (rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)), hypertension, tumor metastasis and development of severe cancers (myeloma, neuroendocrine tumors, lung, and breast cancer) [1,2,3] are major health problems. The second leading cause of death worldwide is cancer and 1 in 6 people die to cancer, accounting for 8.8 million deaths in 2015 [4]. The prevalence of all these diseases is increasing and, in many cases, sufficient therapies are not available. An interest in utilizing the body’s own molecules to treat these diseases arose. CgA is proteolytically cleaved, both intracellularly as well as extracellularly after its release, and this gives rise to several peptides [7, 8]. These peptides exert a broad spectrum of regulatory functions among the metabolic, endocrine, cardiovascular and immune systems [9]. It is becoming increasingly clear that one of these cleavage products, the bio-active peptide catestatin

Objectives

Findings

Conclusion