Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis
| Autor: | Lisa Maccio-Maretto, Angela A. S. Sena, Silvia G. Correa, Sonia Maria Oliani, Bibiana Elisabeth Barrios, Sandra Helena Poliselli Farsky, Marina de Paula-Silva |
|---|---|
| Přispěvatelé: | Universidade Federal de São Paulo (UNIFESP), Cordoba National University (UNC), Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP) |
| Rok vydání: | 2016 |
| Předmět: |
BIOMARKER
0301 basic medicine endocrine system CIENCIAS MÉDICAS Y DE LA SALUD TNF-a Inmunología THERAPY Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Gastrointestinal Agents Intestinal mucosa INFLIXIMAB Animals Medicine Intestinal Mucosa Colitis Acute colitis Annexin A1 Peroxidase Pharmacology Mice Inbred BALB C Gastrointestinal agent Caspase 3 Tumor Necrosis Factor-alpha business.industry Dextran Sulfate purl.org/becyt/ford/3.1 [https] medicine.disease Infliximab Medicina Básica 030104 developmental biology Apoptosis TNF-α Immunology ANNEXIN A1 purl.org/becyt/ford/3 [https] Female Tumor necrosis factor alpha business COLITE ULCERATIVA Biomarkers COLITIS 030215 immunology medicine.drug |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 0006-2952 |
| Popis: | 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. Fil: De Paula Silva, Marina. Universidade de Sao Paulo; Brasil Fil: Barrios, Bibiana Elisabet. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Maccio Maretto, Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Sena, Angela. Universidade de Sao Paulo; Brasil Fil: Poliselli Farsky, Sandra Helena. Universidade de Sao Paulo; Brasil Fil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Oliani, Sonia María. Universidade de Sao Paulo; Brasil |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect