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Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis.
de Paula-Silva, Marina; Barrios, Bibiana Elisabeth; Macció-Maretto, Lisa; Sena, Angela Aparecida; Farsky, Sandra Helena Poliselli; Correa, Silvia Graciela; Oliani, Sonia Maria.
Afiliação
  • de Paula-Silva M; Post-graduation in Structural and Functional Biology, São Paulo Federal University (UNIFESP), São Paulo, São Paulo, Brazil.
  • Barrios BE; Center of Investigation in Biochemistry and Clinical Immunology, Cordoba National University (UNC), Córdoba, Córdoba, Argentina.
  • Macció-Maretto L; Center of Investigation in Biochemistry and Clinical Immunology, Cordoba National University (UNC), Córdoba, Córdoba, Argentina.
  • Sena AA; Department of Biology, Laboratory of Immunomorphology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.
  • Farsky SH; Department of Clinical and Toxicological Analyses, University of São Paulo (USP), São Paulo, São Paulo, Brazil.
  • Correa SG; Center of Investigation in Biochemistry and Clinical Immunology, Cordoba National University (UNC), Córdoba, Córdoba, Argentina.
  • Oliani SM; 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.b
Biochem Pharmacol ; 115: 104-13, 2016 09 01.
Article em En | MEDLINE | ID: mdl-27343762
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fármacos Gastrointestinais / Fator de Necrose Tumoral alfa / Anexina A1 / Colite / Infliximab Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Biochem Pharmacol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fármacos Gastrointestinais / Fator de Necrose Tumoral alfa / Anexina A1 / Colite / Infliximab Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Biochem Pharmacol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido