Dysregulation of Anti-Inflammatory Annexin A1 Expression in Progressive Crohns Disease

dc.contributor.authorSena, Angela
dc.contributor.authorGrishina, Irina
dc.contributor.authorThai, Anne
dc.contributor.authorGoulart, Larissa
dc.contributor.authorMacal, Monica
dc.contributor.authorFenton, Anne
dc.contributor.authorLi, Jay
dc.contributor.authorPrindiville, Thomas
dc.contributor.authorOliani, Sonia Maria [UNESP]
dc.contributor.authorDandekar, Satya
dc.contributor.authorGoulart, Luiz
dc.contributor.authorSankaran-Walters, Sumathi
dc.contributor.institutionUniv Calif Davis
dc.contributor.institutionUniversidade Federal de Uberlândia (UFU)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-12-03T13:11:05Z
dc.date.available2014-12-03T13:11:05Z
dc.date.issued2013-10-10
dc.description.abstractBackground: Development of inflammatory bowel disease (IBD) involves the interplay of environmental and genetic factors with the host immune system. Mechanisms contributing to immune dysregulation in IBD are not fully defined. Development of novel therapeutic strategies is focused on controlling aberrant immune response in IBD. Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD. However, the role of immunomodulatory factors such as annexin A1 (ANXA1) is not well understood. The goal of this study was to examine the association between ANXA1 and IBD, and the effects of anti-TNF-alpha, Infliximab (IFX), therapy on ANXA1 expression.Methods: ANXA1 and TNF-alpha transcript levels in PBMC were measured by RT PCR. Clinical follow up included the administration of serial ibdQs. ANXA1 expression in the gut mucosa was measured by IHC. Plasma ANXA1 levels were measured by ELISA.Results: We found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients. ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders. The IFX therapy also modified the cellular immune activation in the peripheral blood of IBD patients. Decreased expression of ANXA1 was detected in the colonic mucosa of IBD patients with incomplete resolution of inflammation during continuous therapy, which correlated with increased levels of TNF-alpha transcripts. Gut mucosal epithelial barrier disruption was evident by increased plasma bacterial 16S levels.Conclusion: Loss of ANXA1 expression may support inflammation during IBD and can serve as a biomarker of disease progression. Changes in ANXA1 levels may be predictive of therapeutic efficacy.en
dc.description.affiliationUniv Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA
dc.description.affiliationUniv Fed Uberlandia, Inst Genet & Biochem, Nanobiotechnol Lab, BR-38400 Uberlandia, MG, Brazil
dc.description.affiliationUniv Calif Davis, UCDHS Div Hepatol & Gastroenterol, Davis, CA 95616 USA
dc.description.affiliationSao Paulo State Univ, Dept Biol, UNESP, Sao Jose Do Rio Preto, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Dept Biol, UNESP, Sao Jose Do Rio Preto, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipNational Institute of Health (NIH)
dc.description.sponsorshipBuilding Interdisciplinary Research Careers in Women's Health award
dc.description.sponsorshipNICHD
dc.description.sponsorshipORWH
dc.description.sponsorshipNIA
dc.description.sponsorshipIdFAPEMIG: APQ-02613-10
dc.description.sponsorshipIdNational Institute of Health (NIH)R01 DK61297
dc.description.sponsorshipIdNational Institute of Health (NIH)AI43274
dc.description.sponsorshipIdBuilding Interdisciplinary Research Careers in Women's Health awardK12 HD051958
dc.format.extent13
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0076969
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 8, n. 10, 13 p., 2013.
dc.identifier.doi10.1371/journal.pone.0076969
dc.identifier.fileWOS000325814200046.pdf
dc.identifier.issn1932-6203
dc.identifier.lattes5102737730539655
dc.identifier.urihttp://hdl.handle.net/11449/112838
dc.identifier.wosWOS:000325814200046
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPLOS ONE
dc.relation.ispartofjcr2.766
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.titleDysregulation of Anti-Inflammatory Annexin A1 Expression in Progressive Crohns Diseaseen
dc.typeArtigo
dcterms.rightsHolderPublic Library Science
unesp.author.lattes5102737730539655
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências Letras e Ciências Exatas, São José do Rio Pretopt

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