Cardiotrophin-1 attenuates experimental colitis in mice.

Abstract

Cardiotrophin-1 (CT-1) holds potent anti-inflammatory, cytoprotective, and anti-apoptotic effects in the liver, kidneys, and heart. In the present study, the role of endogenous CT-1 and the effect of exogenous CT-1 were evaluated in experimental ulcerative colitis. Colitis was induced in CT-1 knockout and wild-type (WT) mice by administration of dextran sulphate sodium (DSS) in the drinking water during 7 days. CT-1 knockout mice showed higher colon damage and disease severity than WT mice. In addition, CT-1 (200 µg/kg/day, iv) or vehicle (as control) was administered during 3 days to WT, colitic mice, starting on day 4 after initiation of DSS. Disease activity index (DAI), inflammatory markers (tumor necrosis factor α (TNF-α), INFγ, IL-17, IL-10, inducible nitric oxide synthase (iNOS)), colon damage, apoptosis (cleaved caspase 3), nuclear factor κB (NFκB) and STAT-3 activation, and bacterial translocation were measured. Compared with mice treated with DSS, mice also treated with exogenous CT-1 showed lower colon damage, DAI, plasma levels of TNFα, colon expression of TNF-α, INFγ, IL-17, iNOS and cleaved caspase 3, higher NFκB and signal transducer and activator of transcription 3 (STAT3) pathways activation, and absence of bacterial translocation. We conclude that endogenous CT-1 plays a role in the defense and repair response of the colon against ulcerative lesions through an anti-inflammatory and anti-apoptotic effect. Supplementation with exogenous CT-1 ameliorates disease symptoms, which opens a potentially new therapeutic strategy for ulcerative colitis.

• Authors: Vanessa Prieto-Vicente, Ana I Sánchez-Garrido, Víctor Blanco-Gozalo, Miguel Arévalo, Enrique García-Sánchez, Daniel López-Montañés, Yaremi Quiros, Francisco J López-Hernández, Antonio Rodríguez-Pérez, José M López-Novoa
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 132 Issue 9 Pg. 985-1001 (05 23 2018) ISSN: 1470-8736 [Electronic] England
• PMID: 29572384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Chemical References

• Cytokines
• Dextran Sulfate
• cardiotrophin 1

Topics

• Animals
• Colitis, Ulcerative (chemically induced, drug therapy, metabolism)
• Cytokines (blood, genetics, therapeutic use)
• Dextran Sulfate
• Drug Evaluation, Preclinical
• Male
• Mice
• Mice, Knockout