Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis

dc.contributor.authorde Paula-Silva, Marina
dc.contributor.authorBarrios, Bibiana Elisabeth
dc.contributor.authorMacció-Maretto, Lisa
dc.contributor.authorSena, Angela Aparecida [UNESP]
dc.contributor.authorFarsky, Sandra Helena Poliselli
dc.contributor.authorCorrea, Silvia Graciela
dc.contributor.authorOliani, Sonia Maria [UNESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionCordoba National University (UNC)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2018-12-11T17:04:04Z
dc.date.available2018-12-11T17:04:04Z
dc.date.issued2016-09-01
dc.description.abstractTNF-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.en
dc.description.affiliationPost-graduation in Structural and Functional Biology São Paulo Federal University (UNIFESP)
dc.description.affiliationCenter of Investigation in Biochemistry and Clinical Immunology Cordoba National University (UNC)
dc.description.affiliationDepartment of Biology Laboratory of Immunomorphology São Paulo State University (UNESP), São José do Rio Preto
dc.description.affiliationDepartment of Clinical and Toxicological Analyses University of São Paulo (USP)
dc.description.affiliationUnespDepartment of Biology Laboratory of Immunomorphology São Paulo State University (UNESP), São José do Rio Preto
dc.format.extent104-113
dc.identifierhttp://dx.doi.org/10.1016/j.bcp.2016.06.012
dc.identifier.citationBiochemical Pharmacology, v. 115, p. 104-113.
dc.identifier.doi10.1016/j.bcp.2016.06.012
dc.identifier.file2-s2.0-84977616995.pdf
dc.identifier.issn1873-2968
dc.identifier.issn0006-2952
dc.identifier.scopus2-s2.0-84977616995
dc.identifier.urihttp://hdl.handle.net/11449/173195
dc.language.isoeng
dc.relation.ispartofBiochemical Pharmacology
dc.relation.ispartofsjr1,832
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectAnnexin A1
dc.subjectBiomarker
dc.subjectColitis
dc.subjectInfliximab
dc.subjectTherapy
dc.subjectTNF-α
dc.titleRole of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitisen
dc.typeArtigo

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