Abstract |
We evaluated whether the lack of TNF-α signaling increases mucosal levels of annexin A1 (AnxA1); the hypothesis stems from previous findings showing that TNF-α neutralization in Crohn's disease patients up-regulates systemic AnxA1 expression. Biopsies from healthy volunteers and patients under anti-TNF-α 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-α receptor 1 KO ( TNFR1-/-) strain with impaired TNF-α 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-α signaling reduction favors the expression and biological activity of AnxA1 in inflamed intestinal mucosa.
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Authors | Angela A Sena, Luciano P Pedrotti, Bibiana E Barrios, Hugo Cejas, Domingo Balderramo, Ana Diller, Silvia G Correa |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 98
Issue 3
Pg. 422-31
(Dec 01 2015)
ISSN: 1873-2968 [Electronic] England |
PMID | 26386311
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Annexin A1
- Receptors, Tumor Necrosis Factor, Type I
- Dextran Sulfate
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Topics |
- Animals
- Annexin A1
(physiology)
- Colitis
(chemically induced, metabolism)
- Dextran Sulfate
(adverse effects)
- Female
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Receptors, Tumor Necrosis Factor, Type I
(genetics, metabolism)
- Signal Transduction
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