期刊
BIOCHEMICAL PHARMACOLOGY
卷 98, 期 3, 页码 422-431出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2015.09.009
关键词
Therapy; DSS-induced colitis; Inflammation; Gut; Epithelium
资金
- Agencia Nacional de Promocion Cientifica y Tecnologica (FONCYT)
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
- Secretaria de Ciencia y Tecnologia (SECyT-UNC)
We evaluated whether the lack of TNF-alpha signaling increases mucosal levels of annexin A1 (AnxA1); the hypothesis stems from previous findings showing that TNF-alpha neutralization in Crohn's disease patients up-regulates systemic AnxA1 expression. Biopsies from healthy volunteers and patients under anti-TNF-alpha therapy with remittent ulcerative colitis (UC) showed higher AnxA1 expression than those with active disease. We also evaluated dextran sulfate sodium (DSS)-acute colitis in TNF-alpha receptor 1 KO (INFR1-/-) strain with impaired TNF-alpha signaling and C57BL/6 (WT) mice. Although both strains developed colitis, TNFR1-/- mice showed early clinical recovery, lower myeloperoxidase (MPO) activity and milder histopathological alterations. Colonic epithelium from control and DSS-treated TNFR1-/- mice showed intense AnxA1 expression and AnxA1+ CD4+ and CD8+ T cells were more frequent in TNFR1-/- animals, suggesting an extra supply of AnxA1. The pan antagonist of AnxA1 receptors exacerbated the colitis outcome in TNFR1-/- mice, supporting the pivotal role of AnxA1 in the early recovery. Our findings demonstrate that the TNF-alpha signaling reduction favors the expression and biological activity of AnxA1 in inflamed intestinal mucosa. (C) 2015 Elsevier Inc. All rights reserved.
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