The anti-inflammatory effects of the Chromogranin A hormone cleavage product catestatin on human monocytes and macrophages

Abstract Objective High levels of the prohormone chromogranin A (CgA) have been detected in the plasma of patients with various cancers and inflammatory diseases such as rheumatic arthritis, inflammatory bowel disease as well as type 1 and 2 diabetes mellitus (T2DM). In contrast, T2DM and hypertensive patients show reduced levels of the CgA-derived peptide catestatin (CST). Here we show the anti-inflammatory effects of CST on human macrophages and phagocyte migration. Method Mouse phagocyte (monocytes and granulocytes) migration was imaged in the cremaster muscle of mice superperfused with buffer containing CST or the chemokine MIP-2. Human blood monocytes were used for in vitro migration to CCL2 and/or CST and macrophage differentiation assays. Macrophages were treated with CST and polarized towards pro-inflammatory or anti-inflammatory phenotypes. Afterwards, cytokine production was measured by ELISA (Il-10, TNF-a, IL-6) and cells were phenotyped by EM and RNA sequencing. Results In vivo and in vitro imaging shows that CST works as a chemo-attractant for monocytes. Interestingly, the combination of CST with the well-known chemoattractant CCL2 results in an anti-inflammatory effect. Moreover, CST treatment of inflammatory macrophages inhibited TNF-α and IL-6 production. Additionally, several proinflammatory gene levels in CST treated macrophages were decreased. Conclusions CST influences monocyte migration and promotes M1-M2 polarization by decreasing expression of pro-inflammatory cytokines and increasing anti-inflammatory cytokine expression. These factors are important for tissue homeostasis, which makes CST an interesting therapeutic target for treatment and/or diagnosis of various metabolic and immune diseases.