Chromofungin (CHR: CHGA47-66) is downregulated in persons with active ulcerative colitis and suppresses pro-inflammatory macrophage function through the inhibition of NF-κB signaling

Chromogranin-A (CHGA) is a prohormone secreted by neuroendocrine cells and is a precursor of several bioactive peptides, which are implicated in different and distinctive biological and immune functions. Chromofungin (CHR: CHGA(47-66)) is a short peptide with antimicrobial effects and encodes from CHGA exon-IV. Inflammatory bowel disease (IBD) is characterized by alterations in the activation of pro inflammatory pathways, pro-inflammatory macrophages (M1), and nuclear transcription factor kappa B (NF-kappa B) signaling leading to the perpetuation of the inflammatory process. Here, we investigated the activity of CHR (CHGA Exon-IV) in persons with active ulcerative colitis (UC) and the underlying mechanisms in dextran sulfate sodium (DSS)-colitis in regard to macrophages activation and migration. Tissue mRNA expression of CHR (CHGA Exon-IV) was down regulated in active UC compared to healthy individuals and negatively correlated with pro-inflammatory macrophages (M1) cytokines, toll-like receptors (TLR)-4, and pNF-kappa B activity. In DSS colitis, CHR (CHGA Exon-IV) expression was reduced, and exogenous CHR treatment decreased the severity of colitis associated with a reduction of M1 macrophages markers and pNF-kappa B. In vitro, CHR treatment reduced macrophages migration, decreased pro-inflammatory cytokines production and pNF-kappa B. Targeting CHR may represent a promising new direction in research to define new therapeutic targets and biomarkers associated with IBD. (C) 2017 Elsevier Inc. All rights reserved.