The N-Terminal Fragment of Chromogranin A, Vasostatin-1 Protects Mice From Acute or Chronic Colitis Upon Oral Administration
Vasostatin-1 (VS-1), the N-terminal fragment of chromogranin A (CgA), decreases the permeability of endothelial cells in vitro and in vivo.
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.
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.
In vitro, VS-1 inhibited increased permeability of IECs induced by interferon-γ and tumor necrosis factor-α. 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.
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 inflammatory cytokines.
KeywordsChromogranin A Vasostatin-1 Intestinal epithelial cells Inflammatory bowel diseases
This work was supported by the Associazione Italiana per la Ricerca sul Cancro.
Conflict of interest
None of the authors has any conflict of interest.
- 21.Blois A, Srebro B, Mandalà M, Corti A, Helle KB, Serck-Hanssen G. The chromogranin A peptide vasostatin-I inhibits gap formation and signal transduction mediated by inflammatory agents in cultured bovine pulmonary and coronary arterial endothelial cells. Regul Pept. 2006;135:78–84.PubMedCrossRefGoogle Scholar
- 36.Sakata A, Yasuda K, Ochiai T, et al. Inhibition of lipopolysaccharide-induced release of interleukin-8 from intestinal epithelial cells by SMA, a novel inhibitor of sphingomyelinase and its therapeutic effect on dextran sulphate sodium-induced colitis in mice. Cell Immunol. 2007;245:24–31.PubMedCrossRefGoogle Scholar
- 47.Zhang XY, De Meester I, Lambeir AM, et al. Study of the enzymatic degradation of vasostatin I and II and their precursor chromogranin A by dipeptidyl peptidase IV using high-performance liquid chromatography/electrospray mass spectrometry. J Mass Spectrom. 1999;34:255–263.PubMedCrossRefGoogle Scholar