Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , |
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 |