Lack of TNFRI signaling enhances annexin A1 biological activity in intestinal inflammation.

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.

• 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)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Annexin A1
• Receptors, Tumor Necrosis Factor, Type I
• Dextran Sulfate

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