The N-terminal fragment of chromogranin A, vasostatin-1 protects mice from acute or chronic colitis upon oral administration

Cristiano Rumio, Giuseppina F. Dusio, Barbara Colombo, Anna Gasparri, Diego Cardani, Fabrizio Marcucci, Angelo Corti

Research output: Contribution to journalArticle

Abstract

Background Vasostatin-1 (VS-1), the N-terminal fragment of chromogranin A (CgA), decreases the permeability of endothelial cells in vitro and in vivo. Aims Here, we investigated whether a similar effect could be observed also on intestinal epithelial cells (IECs) in vitro and whether VS-1 could have favorable effects on animal models of acute or chronic colitis, which are characterized by increased permeability of the intestinal epithelium. Methods In vitro, VS-1 was tested on IEC monolayers showing increased permeability, on mechanically injured IEC monolayers, and on the production of the chemokine IL-8/KC by lipopolysaccharide (LPS)-stimulated IECs. In vivo, VS-1 was tested in animal models of dextran sodium salt (DSS)-induced acute or chronic colitis. Results In vitro, VS-1 inhibited increased permeability of IECs induced by interferon-c and tumor necrosis factor-a. Moreover, VS-1 promoted healing of mechanically injured IEC monolayers, most likely through stimulation of cell migration, rather than cell proliferation. Eventually, VS-1 inhibited LPS-induced production of IL-8. In vivo, VS-1 exerted protective effects in animal models of acute or chronic colitis upon oral, but not systemic administration. Conclusions VS-1 is therapeutically active in animal models of acute or chronic, DSS-induced colitis. The mechanisms underlying this effect are likely to be multiple, and may include inhibition of enhanced intestinal permeability, repair of injured intestinal mucosae, and inhibition of the production of IL-8/KC and possibly other infammatory cytokines.

Original languageEnglish
Pages (from-to)1227-1237
Number of pages11
JournalDigestive Diseases and Sciences
Volume57
Issue number5
DOIs
Publication statusPublished - May 2012

Keywords

  • Chromogranin A
  • Inflammatory bowel diseases
  • Intestinal epithelial cells
  • Vasostatin-1

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

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