Pivotal Role of Toll-Like Receptors 2 and 4, Its Adaptor Molecule MyD88, and Inflammasome Complex in Experimental Tubule-Interstitial Nephritis

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorCORREA-COSTA, Matheus
dc.contributor.authorBRAGA, Tarcio Teodoro
dc.contributor.authorSEMEDO, Patricia
dc.contributor.authorHAYASHIDA, Caroline Yuri
dc.contributor.authorBECHARA, Luiz Roberto Grassmann
dc.contributor.authorELIAS, Rosa Maria
dc.contributor.authorBARRETO, Claudiene Rodrigues
dc.contributor.authorSILVA-CUNHA, Claudia
dc.contributor.authorHYANE, Meire Ioshie
dc.contributor.authorGONCALVES, Giselle Martins
dc.contributor.authorBRUM, Patricia Chakur
dc.contributor.authorFUJIHARA, Clarice
dc.contributor.authorZATZ, Roberto
dc.contributor.authorPACHECO-SILVA, Alvaro
dc.contributor.authorZAMBONI, Dario S.
dc.contributor.authorCAMARA, Niels Olsen Saraiva
dc.date.accessioned2017-11-27T16:23:29Z
dc.date.available2017-11-27T16:23:29Z
dc.date.issued2011
dc.description.abstractTubule-interstitial nephritis (TIN) results in decreased renal function and interstitial inflammation, which ultimately leads to fibrosis. Excessive adenine intake can cause TIN because xanthine dehydrogenase (XDH) can convert this purine into an insoluble compound, which precipitates in the tubuli. Innate immune sensors, such as Toll-like receptors (TLR) and inflammasome complex, play a crucial role in the initiation of inflammation. The aim of this study was to evaluate the roles of TLR-2 and -4, Myd88 and inflammasome complex in an experimental model of TIN. Here, we show that wild-type (WT) mice fed adenine-enriched food exhibited significant renal dysfunction and enhanced cellular infiltration accompanied by collagen deposition. They also presented higher gene and protein expression of pro-inflammatory cytokines. In contrast, TLR-2, -4, MyD88, ASC and Caspase-1 KO mice showed renoprotection associated with expression of inflammatory molecules at levels comparable to controls. Furthermore, treatment of WT animals with allopurinol, an XDH inhibitor, led to reduced levels of uric acid, oxidative stress, collagen deposition and a downregulation of the NF-kB signaling pathway. We concluded that MyD88 signaling and inflammasome participate in the development of TIN. Furthermore, inhibition of XDH seems to be a promising way to therapeutically target the developing inflammatory process.
dc.description.indexMEDLINE
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo [07/07139-3, 09/54474-8]
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior
dc.description.sponsorshipNational Institute for Science and Technology - Complex Fluids
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico
dc.identifier.citationPLOS ONE, v.6, n.12, article ID e29004, 7p, 2011
dc.identifier.doi10.1371/journal.pone.0029004
dc.identifier.issn1932-6203
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/22601
dc.language.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.ispartofPlos One
dc.rightsopenAccess
dc.rights.holderCopyright PUBLIC LIBRARY SCIENCE
dc.subject.otherxanthine oxidoreductase
dc.subject.otherkidney-disease
dc.subject.othermouse model
dc.subject.otheruric-acid
dc.subject.otherfibrosis
dc.subject.otherdanger
dc.subject.otherinjury
dc.subject.otherdehydrogenase
dc.subject.otheroxidase
dc.subject.wosMultidisciplinary Sciences
dc.titlePivotal Role of Toll-Like Receptors 2 and 4, Its Adaptor Molecule MyD88, and Inflammasome Complex in Experimental Tubule-Interstitial Nephritis
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalCORREA-COSTA, Matheus:Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, Brazil
hcfmusp.author.externalBRAGA, Tarcio Teodoro:Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, Brazil
hcfmusp.author.externalSEMEDO, Patricia:Univ Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, Brazil
hcfmusp.author.externalHAYASHIDA, Caroline Yuri:Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, Brazil
hcfmusp.author.externalBECHARA, Luiz Roberto Grassmann:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil
hcfmusp.author.externalELIAS, Rosa Maria:Univ Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, Brazil
hcfmusp.author.externalBARRETO, Claudiene Rodrigues:Univ Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, Brazil
hcfmusp.author.externalSILVA-CUNHA, Claudia:Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, Brazil
hcfmusp.author.externalHYANE, Meire Ioshie:Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, Brazil
hcfmusp.author.externalGONCALVES, Giselle Martins:Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, Brazil
hcfmusp.author.externalBRUM, Patricia Chakur:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil
hcfmusp.author.externalPACHECO-SILVA, Alvaro:Univ Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, Brazil; Albert Einstein Hosp, Renal Transplantat Unit, Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo, Brazil
hcfmusp.author.externalZAMBONI, Dario S.:Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Cell Biol, Sao Paulo, Brazil
hcfmusp.author.externalCAMARA, Niels Olsen Saraiva:Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, Brazil; Univ Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, Brazil
hcfmusp.citation.scopus81
hcfmusp.contributor.author-fmusphcCLARICE KAZUE FUJIHARA
hcfmusp.contributor.author-fmusphcROBERTO ZATZ
hcfmusp.description.articlenumbere29004
hcfmusp.description.issue12
hcfmusp.description.volume6
hcfmusp.origemWOS
hcfmusp.origem.pubmed22194975
hcfmusp.origem.scopus2-s2.0-83355168710
hcfmusp.origem.wosWOS:000298369100139
hcfmusp.publisher.citySAN FRANCISCO
hcfmusp.publisher.countryUSA
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