title: 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.affiliation: Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Cordoba, Córdoba, Argentina.
authors.forename: Angela A
authors.initials: AA
authors.lastname: Sena
authors.affiliation: Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Cordoba, Córdoba, Argentina.
authors.forename: Luciano P
authors.initials: LP
authors.lastname: Pedrotti
authors.affiliation: Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Cordoba, Córdoba, Argentina.
authors.forename: Bibiana E
authors.initials: BE
authors.lastname: Barrios
authors.affiliation: Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Cordoba, Córdoba, Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cejas
authors.affiliation: Gastroenterology Department, Hospital Privado, Centro Médico, Córdoba, Argentina.
authors.forename: Domingo
authors.initials: D
authors.lastname: Balderramo
authors.affiliation: Pathology Department, Hospital Privado, Centro Médico, Córdoba, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Diller
authors.affiliation: Immunology, Department of Clinical Biochemistry, CIBICI (CONICET), Faculty of Chemical Sciences, National University of Cordoba, Córdoba, Argentina. Electronic address: scorrea@fcq.unc.edu.ar.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Correa
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000502:physiology*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D016264:Dextran Sulfate / Q000009:adverse effects; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017305:Annexin A1; D047888:Receptors, Tumor Necrosis Factor, Type I; D016264:Dextran Sulfate
keywords: DSS-induced colitis; Epithelium; Gut; Inflammation; Therapy