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

• Published in: Biochemical pharmacology Vol. 98; no. 3; pp. 422 - 431
• Main Authors: Sena, Angela A., Pedrotti, Luciano P., Barrios, Bibiana E., Cejas, Hugo, Balderramo, Domingo, Diller, Ana, Correa, Silvia G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.12.2015
• Subjects: Animals; Annexin A1 - physiology; Colitis - chemically induced; Colitis - metabolism; Dextran Sulfate - adverse effects; DSS-induced colitis; Epithelium; Female; Gut; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Tumor Necrosis Factor, Type I - genetics; Receptors, Tumor Necrosis Factor, Type I - metabolism; Signal Transduction; Therapy; Therapy; DSS-induced colitis; Inflammation; Epithelium; Gut
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2015.09.009

[Display omitted] 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.