TLR4 deficiency upregulates TLR9 expression and enhances irinotecan-related intestinal mucositis and late-onset diarrhoea

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorFederal University of Ceará-
Autor(es): dc.contributorCancer Institute of Ceará (ICC)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorWong, Deysi Viviana Tenazoa-
Autor(es): dc.creatorHolanda, Renata Brito Falcão-
Autor(es): dc.creatorCajado, Aurilene Gomes-
Autor(es): dc.creatorBandeira, Alessandro Maia-
Autor(es): dc.creatorPereira, Jorge Fernando Bessa-
Autor(es): dc.creatorAmorim, Joice Oliveira-
Autor(es): dc.creatorTorres, Clarice Sampaio-
Autor(es): dc.creatorFerreira, Luana Maria Moura-
Autor(es): dc.creatorLopes, Marina Helena Silva-
Autor(es): dc.creatorOliveira, Roberta Taiane Germano-
Autor(es): dc.creatorPereira, Anamaria Falcão-
Autor(es): dc.creatorSant'Ana, Rosane Oliveira-
Autor(es): dc.creatorArruda, Larissa Mont'alverne-
Autor(es): dc.creatorRibeiro-Júnior, Howard Lopes-
Autor(es): dc.creatorPinheiro, Ronald Feitosa-
Autor(es): dc.creatorAlmeida, Paulo Roberto Carvalho-
Autor(es): dc.creatorCarvalho, Robson Francisco-
Autor(es): dc.creatorChaves, Fábio Figueiredo-
Autor(es): dc.creatorRocha-Filho, Duílio Reis-
Autor(es): dc.creatorCunha, Fernando Queiroz-
Autor(es): dc.creatorLima-Júnior, Roberto César Pereira-
Data de aceite: dc.date.accessioned2025-08-21T16:52:27Z-
Data de disponibilização: dc.date.available2025-08-21T16:52:27Z-
Data de envio: dc.date.issued2022-05-01-
Data de envio: dc.date.issued2022-05-01-
Data de envio: dc.date.issued2021-10-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1111/bph.15609-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/233336-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/233336-
Descrição: dc.descriptionBackground and purpose: Severe diarrhoea, a common gastrointestinal manifestation of anticancer treatment with irinotecan, might involve single nucleotide polymorphisms (SNPs) of toll-like receptors (TLRs), described as critical bacterial sensors in the gut. Here, colorectal cancer patients carrying missense TLR4 A896G (rs4986790) or C1,196T (rs4986791) SNPs and Tlr4 knockout (Tlr4−/−) mice were given irinotecan to investigate the severity of the induced diarrhoea. Experimental approach: Forty-six patients treated with irinotecan-based regimens had diarrhoea severity analysed according to TLR4 genotypes. In the experimental setting, wild-type (WT) or Tlr4−/− mice were given irinotecan (45 or 75 mg·kg−1, i.p.) or saline (3 ml·kg−1). Diarrhoea severity was evaluated by measuring intestinal injury and inflammatory markers expression after animals were killed. Key results: All patients with TLR4 SNPs chemotherapy-treated presented diarrhoea, whereas gastrointestinal toxicity was observed in 50% of the wild homozygous individuals. Mice injected with irinotecan presented systemic bacterial translocation and increased TLR4 immunostaining in the intestine. In line with the clinical findings, Tlr4 gene deficiency enhanced irinotecan-related diarrhoea and TLR9 expression in mice. An increased myeloperoxidase activity and Il-18 expression along with IL-10 decreased production in Tlr4−/− mice also indicated an intensified intestinal damage and inflammatory response. Conclusion and implications: TLR4 deficiency upregulates TLR9 expression and enhances intestinal damage and the severity of late-onset diarrhoea during irinotecan-based treatment. Identifying patients genetically predisposed to chemotherapy-associated diarrhoea is a strategy toward precision medicine.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico-
Descrição: dc.descriptionGraduate Program in Pathology Department of Pathology and Forensic Medicine Faculty of Medicine Federal University of Ceará-
Descrição: dc.descriptionLaboratory of Molecular Biology and Genetics Haroldo Juaçaba Hospital Cancer Institute of Ceará (ICC)-
Descrição: dc.descriptionGraduate Program in Pharmaceutical Sciences Department of Pharmacy Faculty of Pharmacy Nursing and Dentistry Federal University of Ceará-
Descrição: dc.descriptionLaboratory of Inflammation and Cancer Pharmacology Drug Research and Development Center (NPDM) Department of Physiology and Pharmacology Federal University of Ceará-
Descrição: dc.descriptionCancer Cytogenomic Laboratory Drug Research and Development Center (NPDM) Federal University of Ceará-
Descrição: dc.descriptionClinical Oncology Service Haroldo Juaçaba Hospital Cancer Institute of Ceará (ICC)-
Descrição: dc.descriptionDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP)-
Descrição: dc.descriptionClinical Oncology Service Walter Cantídio University Hospital Federal University of Ceará-
Descrição: dc.descriptionDepartment of Pharmacology School of Medicine of Ribeirão Preto University of São Paulo-
Descrição: dc.descriptionDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP)-
Descrição: dc.descriptionCNPq: 310568/2017-0-
Descrição: dc.descriptionCNPq: 421202/2018-1-
Descrição: dc.descriptionCAPES: CAPES-PROEX 0756/2020-
Descrição: dc.descriptionFundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico: PR2-0101-00054.01.00/15-
Formato: dc.format4193-4209-
Idioma: dc.languageen-
Relação: dc.relationBritish Journal of Pharmacology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectcolorectal cancer-
Palavras-chave: dc.subjectdiarrhoea-
Palavras-chave: dc.subjectintestinal mucosa-
Palavras-chave: dc.subjectirinotecan-
Palavras-chave: dc.subjectmucositis-
Palavras-chave: dc.subjectsingle nucleotide polymorphism-
Palavras-chave: dc.subjecttoll-like receptor 4-
Título: dc.titleTLR4 deficiency upregulates TLR9 expression and enhances irinotecan-related intestinal mucositis and late-onset diarrhoea-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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