Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer

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dc.contributor.authorChuffa, Luiz Gustavo de Almeida [UNESP]
dc.contributor.authorFioruci-Fontanelli, Beatriz Aparecida [UNESP]
dc.contributor.authorMendes, Leonardo de Oliveira [UNESP]
dc.contributor.authorSeiva, Fábio Rodrigues Ferreira
dc.contributor.authorMartinez, Marcelo
dc.contributor.authorFavaro, Wagner José
dc.contributor.authorDomeniconi, Raquel Fantin [UNESP]
dc.contributor.authorPinheiro, Patricia Fernanda Felipe [UNESP]
dc.contributor.authorSantos, Lucilene Delazari dos [UNESP]
dc.contributor.authorMartinez, Francisco Eduardo
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Estadual do Norte do Paraná (UENP)
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.date.accessioned2015-10-21T13:10:52Z
dc.date.available2015-10-21T13:10:52Z
dc.date.issued2015-02-06
dc.description.abstractBackground: Toll-like receptors (TLRs) are effector molecules expressed on the surface of ovarian cancer (OC) cells, but the functions of the TLR2/TLR4 signaling pathways in these cells remain unclear. Melatonin (mel) acts as an anti-inflammatory factor and has been reported to modulate TLRs in some aggressive tumor cell types. Therefore, we investigated OC and the effect of long-term mel therapy on the signaling pathways mediated by TLR2 and TLR4 via myeloid differentiation factor 88 (MyD88) and toll-like receptor-associated activator of interferon (TRIF) in an ethanol-preferring rat model.Methods: To induce OC, the left ovary of animals either consuming 10% (v/v) ethanol or not was injected directly under the bursa with a single dose of 100 mu g of 7,12-dimethylbenz(a) anthracene (DMBA) dissolved in 10 mu L of sesame oil. The right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of mel (200 mu g/100 g b.w./day) for 60 days.Results: Although mel therapy was unable to reduce TLR2 levels, it was able to suppress the OC-associated increase in the levels of the following proteins: TLR4, MyD88, nuclear factor kappa B (NFkB p65), inhibitor of NFkB alpha (IkB alpha), IkB kinase alpha (IKK-alpha), TNF receptor-associated factor 6 (TRAF6), TRIF, interferon regulatory factor 3 (IRF3), interferon beta (IFN-beta), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-6. In addition, mel significantly attenuated the expression of IkB alpha, NFkB p65, TRIF and IRF-3, which are involved in TLR4-mediated signaling in OC during ethanol intake.Conclusion: Collectively, our results suggest that mel attenuates the TLR4-induced MyD88- and TRIF-dependent signaling pathways in ethanol-preferring rats with OC.en
dc.description.affiliationUniversidade Estadual do Norte do Paraná, Instituto de Biologia, Campus Luiz Meneghel
dc.description.affiliationUniversidade Federal de São Carlos, Departamento de Morfologia e Patologia
dc.description.affiliationUniversidade Estadual de Campinas, Departamento de Anatomia, Biologia Celular e Fisiologia e Biofísica, Instituto de Biologia
dc.description.affiliationUnespUniversidade Estadual Paulista, Departamento de Anatomia, Instituto de Biociências de Botucatu
dc.description.affiliationUnespUniversidade Estadual Paulista, Centro de Venenos e Animais Peçonhentos de Botucatu
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2011/19294-9
dc.description.sponsorshipIdFAPESP: 2013/02466-7
dc.format.extent1-13
dc.identifierhttp://www.biomedcentral.com/1471-2407/15/34
dc.identifier.citationBmc Cancer. London: Biomed Central Ltd, v. 15, p. 1-13, 2015.
dc.identifier.doi10.1186/s12885-015-1032-4
dc.identifier.fileWOS000349182200001.pdf
dc.identifier.issn1471-2407
dc.identifier.lattes5121319676503034
dc.identifier.lattes5481756528299469
dc.identifier.lattes1739564105219382
dc.identifier.lattes5760560970751598
dc.identifier.lattes3368404126695911
dc.identifier.orcid0000-0003-1452-5708
dc.identifier.orcid0000-0003-2938-010X
dc.identifier.urihttp://hdl.handle.net/11449/128549
dc.identifier.wosWOS:000349182200001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Cancer
dc.relation.ispartofjcr3.288
dc.relation.ispartofsjr1,464
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectOvarian canceren
dc.subjectMelatoninen
dc.subjectInflammationen
dc.subjectTLR4en
dc.subjectMyD88en
dc.subjectTRIFen
dc.titleMelatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian canceren
dc.typeArtigo
dcterms.rightsHolderBiomed Central Ltd
unesp.advisor.lattes3368404126695911
unesp.author.lattes5121319676503034
unesp.author.lattes1739564105219382
unesp.author.lattes5760560970751598[8]
unesp.author.lattes5481756528299469[7]
unesp.author.orcid0000-0002-7461-8773[4]
unesp.author.orcid0000-0001-5830-8938[6]
unesp.author.orcid0000-0003-1452-5708[8]
unesp.author.orcid0000-0003-2938-010X[7]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt

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