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

Detalhes bibliográficos
Autor(a) principal: Chuffa, Luiz Gustavo de Almeida [UNESP]
Data de Publicação: 2015
Outros Autores: Fioruci-Fontanelli, Beatriz Aparecida [UNESP], Mendes, Leonardo de Oliveira [UNESP], Seiva, Fábio Rodrigues Ferreira, Martinez, Marcelo, Favaro, Wagner José, Domeniconi, Raquel Fantin [UNESP], Pinheiro, Patricia Fernanda Felipe [UNESP], Santos, Lucilene Delazari dos [UNESP], Martinez, Francisco Eduardo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://www.biomedcentral.com/1471-2407/15/34
http://hdl.handle.net/11449/128549
Resumo: Background: 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.
id UNSP_39feb68e79593f351e00fa4ff14cb47c
oai_identifier_str oai:repositorio.unesp.br:11449/128549
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancerOvarian cancerMelatoninInflammationTLR4MyD88TRIFBackground: 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Estadual do Norte do Paraná, Instituto de Biologia, Campus Luiz MeneghelUniversidade Federal de São Carlos, Departamento de Morfologia e PatologiaUniversidade Estadual de Campinas, Departamento de Anatomia, Biologia Celular e Fisiologia e Biofísica, Instituto de BiologiaUniversidade Estadual Paulista, Departamento de Anatomia, Instituto de Biociências de BotucatuUniversidade Estadual Paulista, Centro de Venenos e Animais Peçonhentos de BotucatuFAPESP: 2011/19294-9FAPESP: 2013/02466-7Biomed Central LtdUniversidade Estadual Paulista (Unesp)Universidade Estadual do Norte do Paraná (UENP)Universidade Federal de São Carlos (UFSCar)Universidade Estadual de Campinas (UNICAMP)Chuffa, Luiz Gustavo de Almeida [UNESP]Fioruci-Fontanelli, Beatriz Aparecida [UNESP]Mendes, Leonardo de Oliveira [UNESP]Seiva, Fábio Rodrigues FerreiraMartinez, MarceloFavaro, Wagner JoséDomeniconi, Raquel Fantin [UNESP]Pinheiro, Patricia Fernanda Felipe [UNESP]Santos, Lucilene Delazari dos [UNESP]Martinez, Francisco Eduardo2015-10-21T13:10:52Z2015-10-21T13:10:52Z2015-02-06info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1-13application/pdfhttp://www.biomedcentral.com/1471-2407/15/34Bmc Cancer. London: Biomed Central Ltd, v. 15, p. 1-13, 2015.1471-2407http://hdl.handle.net/11449/12854910.1186/s12885-015-1032-4WOS:000349182200001WOS000349182200001.pdf512131967650303454817565282994691739564105219382576056097075159833684041266959110000-0003-1452-57080000-0003-2938-010XWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBmc Cancer3.2881,464info:eu-repo/semantics/openAccess2023-10-28T06:07:52Zoai:repositorio.unesp.br:11449/128549Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:15:14.851437Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
title Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
spellingShingle Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
Chuffa, Luiz Gustavo de Almeida [UNESP]
Ovarian cancer
Melatonin
Inflammation
TLR4
MyD88
TRIF
title_short Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
title_full Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
title_fullStr Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
title_full_unstemmed Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
title_sort Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
author Chuffa, Luiz Gustavo de Almeida [UNESP]
author_facet Chuffa, Luiz Gustavo de Almeida [UNESP]
Fioruci-Fontanelli, Beatriz Aparecida [UNESP]
Mendes, Leonardo de Oliveira [UNESP]
Seiva, Fábio Rodrigues Ferreira
Martinez, Marcelo
Favaro, Wagner José
Domeniconi, Raquel Fantin [UNESP]
Pinheiro, Patricia Fernanda Felipe [UNESP]
Santos, Lucilene Delazari dos [UNESP]
Martinez, Francisco Eduardo
author_role author
author2 Fioruci-Fontanelli, Beatriz Aparecida [UNESP]
Mendes, Leonardo de Oliveira [UNESP]
Seiva, Fábio Rodrigues Ferreira
Martinez, Marcelo
Favaro, Wagner José
Domeniconi, Raquel Fantin [UNESP]
Pinheiro, Patricia Fernanda Felipe [UNESP]
Santos, Lucilene Delazari dos [UNESP]
Martinez, Francisco Eduardo
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade Estadual do Norte do Paraná (UENP)
Universidade Federal de São Carlos (UFSCar)
Universidade Estadual de Campinas (UNICAMP)
dc.contributor.author.fl_str_mv Chuffa, Luiz Gustavo de Almeida [UNESP]
Fioruci-Fontanelli, Beatriz Aparecida [UNESP]
Mendes, Leonardo de Oliveira [UNESP]
Seiva, Fábio Rodrigues Ferreira
Martinez, Marcelo
Favaro, Wagner José
Domeniconi, Raquel Fantin [UNESP]
Pinheiro, Patricia Fernanda Felipe [UNESP]
Santos, Lucilene Delazari dos [UNESP]
Martinez, Francisco Eduardo
dc.subject.por.fl_str_mv Ovarian cancer
Melatonin
Inflammation
TLR4
MyD88
TRIF
topic Ovarian cancer
Melatonin
Inflammation
TLR4
MyD88
TRIF
description Background: 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-10-21T13:10:52Z
2015-10-21T13:10:52Z
2015-02-06
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://www.biomedcentral.com/1471-2407/15/34
Bmc Cancer. London: Biomed Central Ltd, v. 15, p. 1-13, 2015.
1471-2407
http://hdl.handle.net/11449/128549
10.1186/s12885-015-1032-4
WOS:000349182200001
WOS000349182200001.pdf
5121319676503034
5481756528299469
1739564105219382
5760560970751598
3368404126695911
0000-0003-1452-5708
0000-0003-2938-010X
url http://www.biomedcentral.com/1471-2407/15/34
http://hdl.handle.net/11449/128549
identifier_str_mv Bmc Cancer. London: Biomed Central Ltd, v. 15, p. 1-13, 2015.
1471-2407
10.1186/s12885-015-1032-4
WOS:000349182200001
WOS000349182200001.pdf
5121319676503034
5481756528299469
1739564105219382
5760560970751598
3368404126695911
0000-0003-1452-5708
0000-0003-2938-010X
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Bmc Cancer
3.288
1,464
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1-13
application/pdf
dc.publisher.none.fl_str_mv Biomed Central Ltd
publisher.none.fl_str_mv Biomed Central Ltd
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808128624517185536