Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.bcp.2016.06.012 http://hdl.handle.net/11449/173195 |
Resumo: | 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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Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitisAnnexin A1BiomarkerColitisInfliximabTherapyTNF-αTNF-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.Post-graduation in Structural and Functional Biology São Paulo Federal University (UNIFESP)Center of Investigation in Biochemistry and Clinical Immunology Cordoba National University (UNC)Department of Biology Laboratory of Immunomorphology São Paulo State University (UNESP), São José do Rio PretoDepartment of Clinical and Toxicological Analyses University of São Paulo (USP)Department of Biology Laboratory of Immunomorphology São Paulo State University (UNESP), São José do Rio PretoUniversidade Federal de São Paulo (UNIFESP)Cordoba National University (UNC)Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)de Paula-Silva, MarinaBarrios, Bibiana ElisabethMacció-Maretto, LisaSena, Angela Aparecida [UNESP]Farsky, Sandra Helena PoliselliCorrea, Silvia GracielaOliani, Sonia Maria [UNESP]2018-12-11T17:04:04Z2018-12-11T17:04:04Z2016-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article104-113application/pdfhttp://dx.doi.org/10.1016/j.bcp.2016.06.012Biochemical Pharmacology, v. 115, p. 104-113.1873-29680006-2952http://hdl.handle.net/11449/17319510.1016/j.bcp.2016.06.0122-s2.0-849776169952-s2.0-84977616995.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBiochemical Pharmacology1,832info:eu-repo/semantics/openAccess2023-11-02T06:14:09Zoai:repositorio.unesp.br:11449/173195Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:45:30.845731Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis |
title |
Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis |
spellingShingle |
Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis de Paula-Silva, Marina Annexin A1 Biomarker Colitis Infliximab Therapy TNF-α |
title_short |
Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis |
title_full |
Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis |
title_fullStr |
Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis |
title_full_unstemmed |
Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis |
title_sort |
Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis |
author |
de Paula-Silva, Marina |
author_facet |
de Paula-Silva, Marina Barrios, Bibiana Elisabeth Macció-Maretto, Lisa Sena, Angela Aparecida [UNESP] Farsky, Sandra Helena Poliselli Correa, Silvia Graciela Oliani, Sonia Maria [UNESP] |
author_role |
author |
author2 |
Barrios, Bibiana Elisabeth Macció-Maretto, Lisa Sena, Angela Aparecida [UNESP] Farsky, Sandra Helena Poliselli Correa, Silvia Graciela Oliani, Sonia Maria [UNESP] |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Cordoba National University (UNC) Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
de Paula-Silva, Marina Barrios, Bibiana Elisabeth Macció-Maretto, Lisa Sena, Angela Aparecida [UNESP] Farsky, Sandra Helena Poliselli Correa, Silvia Graciela Oliani, Sonia Maria [UNESP] |
dc.subject.por.fl_str_mv |
Annexin A1 Biomarker Colitis Infliximab Therapy TNF-α |
topic |
Annexin A1 Biomarker Colitis Infliximab Therapy TNF-α |
description |
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. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-09-01 2018-12-11T17:04:04Z 2018-12-11T17:04:04Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.bcp.2016.06.012 Biochemical Pharmacology, v. 115, p. 104-113. 1873-2968 0006-2952 http://hdl.handle.net/11449/173195 10.1016/j.bcp.2016.06.012 2-s2.0-84977616995 2-s2.0-84977616995.pdf |
url |
http://dx.doi.org/10.1016/j.bcp.2016.06.012 http://hdl.handle.net/11449/173195 |
identifier_str_mv |
Biochemical Pharmacology, v. 115, p. 104-113. 1873-2968 0006-2952 10.1016/j.bcp.2016.06.012 2-s2.0-84977616995 2-s2.0-84977616995.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Biochemical Pharmacology 1,832 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
104-113 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128697208668160 |