Cardiotrophin-1 attenuates experimental colitis in mice

In this 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 knock-out and wild type mice by administration of dextran sodium sulphate (DSS) in the drinking water during 7 days. CT-1 knock-out mice showed higher colon damage and disease severity than wild type mice. In addition, CT-1 (200 µg/kg/day, iv) or vehicle (as control) were administered during 3 days to wild type, colitic mice, starting on day 4 after initiation of DSS. Disease activity index (DAI), inflammatory markers (TNF-α, INF, IL-17, IL-10, iNOS), colon damage, apoptosis (cleaved caspase-3), NFB and STAT-3 activation, and bacterial translocation were measured. Compared with mice treated with DSS, mice treated also with exogenous CT-1 showed lower colon damage, DAI, plasma levels of TNFα, colon expression of TNF-α, INF, IL-17, iNOS and cleaved caspase 3, higher NFB and STAT3 pathways activation, and absence of bacterial translocation, compared with untreated colitic mice. 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.

Source: Clinical Science - March 23, 2018 Category: Biomedical Science Authors: Prieto-Vicente, V., Sanchez-Garrido, A. I., Blanco-Gozalo, V., Arevalo, M., Garcia-Sanchez, E. M., Lopez-Montanes, D., Quiros, Y., Lopez-Hernandez, F. J., Rodriguez-Perez, A., Lopez-Novoa, J. M. Tags: PublishAheadOfPrint Source Type: research