| First Author | Sena AA | Year | 2015 |
| Journal | Biochem Pharmacol | Volume | 98 |
| Issue | 3 | Pages | 422-31 |
| PubMed ID | 26386311 | Mgi Jnum | J:228431 |
| Mgi Id | MGI:5707089 | Doi | 10.1016/j.bcp.2015.09.009 |
| Citation | Sena AA, et al. (2015) Lack of TNFRI signaling enhances annexin A1 biological activity in intestinal inflammation. Biochem Pharmacol 98(3):422-31 |
| abstractText | 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 (TNFR1-/-) 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. |
