Ulcerative colitis (UC) is characterized by aberrant regulation of tight junctions (TJ),
signal transducer and activator of transcription 3 (STAT3), and
interleukin (IL)-8/18, which lead to intestinal barrier defects.
Catestatin (CST), an enterochromaffin-derived
peptide, regulates immune communication and STAT-3 in the inflamed intestine. Here, we investigated the effects of CST during the development of
inflammation using human biopsies from patients with active UC, human colonic epithelial cells (Caco2), and an experimental model of UC (
dextran sulfate sodium [DSS]-
colitis). In UC patients, the
protein and
mRNA level of CST was significantly decreased. Colonic expression of CST showed a strong positive linear relationship with TJ
proteins and STAT3, and a strong negative correlation with
IL-8 and
IL-18. Intra-
rectal administration of CST reduced the severity of experimental
colitis,
IL-18 colonic levels, maintained TJ
proteins and enhanced the phosphorylation of STAT3. CST administration increased proliferation, viability, migration, TJ
proteins, and p-STAT3 levels, and reduced
IL-8 &
amp;
IL-18 in LPS- &
amp; DSS-induced Caco2 cell epithelial injury, and the presence of STAT-3 inhibitor abolished the beneficial effect of CST. In inflammatory conditions, we conclude that CST could regulate intestinal mucosal dynamic via a potential STAT3-dependent pathway that needs to be further defined. Targeting CST in intestinal epithelial cells (IECs) should be a promising therapeutic approach such as when intestinal epithelial cell homeostasis is compromised in UC patients.