title: Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis.
abstract: TNF-α is involved in the mechanisms that initiate inflammatory bowel diseases (IBDs). Anti-TNF-α drugs, such as infliximab (IFX), cause non-responsiveness and side effects, indicating the need to investigate alternative therapies for these diseases. The anti-inflammatory protein, annexin A1 (AnxA1), has been associated with the protection of the gastrointestinal mucosa. To further address the role of endogenous AnxA1 on the TNF-α blockade efficacy in a murine model, we assessed colitis induced by Dextran Sulfate Sodium (DSS) in wild-type (WT) and AnxA1(-/-) Balb/c mice treated with IFX. We consistently observed endogenous AnxA1 prevented clinical and physiological manifestations of experimental colitis treated with IFX, additionally the manifestation of the disease was observed earlier in AnxA1(-)(/-) mice. Rectal bleeding, diarrhea, histological score, epithelial damages and collagen degradation caused by DSS were prevented following IFX treatment only in WT mice. IL-6 increased during colitis in WT and AnxA1(-)(/-) mice, decreasing under IFX treatment in WT. The influx of neutrophils and TNF-α secretion were largely elevated in AnxA1(-)(/-) mice when compared to WT mice. In the group WT/DSS+IFX, phagocytes were more susceptible to apoptosis following treatment with IFX. Endogenous expression of AnxA1 increased after DSS and decreased with IFX treatment, demonstrating an attenuated inflammatory response. The data indicate that AnxA1 contributes to the establishment of intestinal homeostasis after blocking of TNF-α was used as a treatment of IBD, constituting a key molecule in the mechanism of action and a potential biomarker of therapeutic efficacy.
authors.affiliation: Post-graduation in Structural and Functional Biology, São Paulo Federal University (UNIFESP), São Paulo, São Paulo, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: de Paula-Silva
authors.affiliation: Center of Investigation in Biochemistry and Clinical Immunology, Cordoba National University (UNC), Córdoba, Córdoba, Argentina.
authors.forename: Bibiana Elisabeth
authors.initials: BE
authors.lastname: Barrios
authors.affiliation: Center of Investigation in Biochemistry and Clinical Immunology, Cordoba National University (UNC), Córdoba, Córdoba, Argentina.
authors.forename: Lisa
authors.initials: L
authors.lastname: Macció-Maretto
authors.affiliation: Department of Biology, Laboratory of Immunomorphology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.
authors.forename: Angela Aparecida
authors.initials: AA
authors.lastname: Sena
authors.affiliation: Department of Clinical and Toxicological Analyses, University of São Paulo (USP), São Paulo, São Paulo, Brazil.
authors.forename: Sandra Helena Poliselli
authors.initials: SH
authors.lastname: Farsky
authors.affiliation: Center of Investigation in Biochemistry and Clinical Immunology, Cordoba National University (UNC), Córdoba, Córdoba, Argentina.
authors.forename: Silvia Graciela
authors.initials: SG
authors.lastname: Correa
authors.affiliation: Post-graduation in Structural and Functional Biology, São Paulo Federal University (UNIFESP), São Paulo, São Paulo, Brazil; Department of Biology, Laboratory of Immunomorphology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil. Electronic address: smoliani@ibilce.unesp.br.
authors.forename: Sonia Maria
authors.initials: SM
authors.lastname: Oliani
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000172:deficiency / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D000069285:Infliximab / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D017305:Annexin A1; D015415:Biomarkers; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D000069285:Infliximab; D009195:Peroxidase; D053148:Caspase 3
keywords: Annexin A1; Biomarker; Colitis; Infliximab; TNF-α; Therapy