Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.archoralbio.2021.105159 http://hdl.handle.net/11449/207761 |
Resumo: | Objective: Oral mucositis (OM), the most common side effect of cancer therapy, is associated with pro-inflammatory cytokines and matrix metalloproteinases (MMPs) increased expression. Although there are approaches for OM management, none is infallible, thus, elucidation of molecular events related to OM etiopathogenesis may improve current therapeutic strategies. This study assessed the influence of pro-inflammatory cytokines and chemotherapy drugs on MMPs expression and synthesis by oral mucosa cells. Design: Human gingival fibroblasts (HGF) were exposed to different concentrations of methotrexate (MTX) and 5-fluorouracil (5-FU); subsequentially, cell viability, nitric oxide and interleukin(IL)-6 production were evaluated to select the concentration of these drugs that could stimulate inflammatory phenotype without cytotoxic effects. Then, HGF and primary gingival keratinocytes (PGK) were subjected to different stimuli: culture medium (negative control), tumor necrosis factor-alpha (TNF-α – positive control), IL-6, IL-8, MTX, and 5-FU for 3, 6, 12, and 24 h. Next, gene expression and synthesis of MMP-2 and MMP-9 by HGF and MMP-3 by PGK were assessed. Results: At 6 h, MMP-2 synthesis increased 60 % after exposure to TNF-α and MTX, 40 % after IL-6, and 15 % after IL-8. At 12 h, MMP-9 synthesis increased 15 % after exposure to TNF-α, while MMP-3 synthesis increased 30 % after TNF-α, and 10 % after IL-8. TNF-α-treated groups presented increased gene expression of all MMPs evaluated. IL-8 and 5-FU increased MMP-2 and MMP-3 expression, while IL-6 and MTX augmented MMP-2 expression. Conclusions: The chemotherapy drugs and cytokines investigated up-regulated MMPs expression by oral mucosa cells, which may lead to OM establishment and severity. |
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Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cellsChemotherapyCytokinesFibroblastsKeratinocytesMatrix metalloproteinasesOral mucositisObjective: Oral mucositis (OM), the most common side effect of cancer therapy, is associated with pro-inflammatory cytokines and matrix metalloproteinases (MMPs) increased expression. Although there are approaches for OM management, none is infallible, thus, elucidation of molecular events related to OM etiopathogenesis may improve current therapeutic strategies. This study assessed the influence of pro-inflammatory cytokines and chemotherapy drugs on MMPs expression and synthesis by oral mucosa cells. Design: Human gingival fibroblasts (HGF) were exposed to different concentrations of methotrexate (MTX) and 5-fluorouracil (5-FU); subsequentially, cell viability, nitric oxide and interleukin(IL)-6 production were evaluated to select the concentration of these drugs that could stimulate inflammatory phenotype without cytotoxic effects. Then, HGF and primary gingival keratinocytes (PGK) were subjected to different stimuli: culture medium (negative control), tumor necrosis factor-alpha (TNF-α – positive control), IL-6, IL-8, MTX, and 5-FU for 3, 6, 12, and 24 h. Next, gene expression and synthesis of MMP-2 and MMP-9 by HGF and MMP-3 by PGK were assessed. Results: At 6 h, MMP-2 synthesis increased 60 % after exposure to TNF-α and MTX, 40 % after IL-6, and 15 % after IL-8. At 12 h, MMP-9 synthesis increased 15 % after exposure to TNF-α, while MMP-3 synthesis increased 30 % after TNF-α, and 10 % after IL-8. TNF-α-treated groups presented increased gene expression of all MMPs evaluated. IL-8 and 5-FU increased MMP-2 and MMP-3 expression, while IL-6 and MTX augmented MMP-2 expression. Conclusions: The chemotherapy drugs and cytokines investigated up-regulated MMPs expression by oral mucosa cells, which may lead to OM establishment and severity.Department of Dental Materials and Prosthodontics São Paulo State University (UNESP) School of Dentistry - AraraquaraDepartment of Orthodontics and Pediatric Dentistry São Paulo State University (UNESP) School of Dentistry - AraraquaraDepartment of Physiology and Pathology São Paulo State University (UNESP) School of Dentistry - AraraquaraDepartment of Dentistry Ribeirão Preto University (UNAERP)Department of Dental Materials and Prosthodontics São Paulo State University (UNESP) School of Dentistry - AraraquaraDepartment of Orthodontics and Pediatric Dentistry São Paulo State University (UNESP) School of Dentistry - AraraquaraDepartment of Physiology and Pathology São Paulo State University (UNESP) School of Dentistry - AraraquaraUniversidade Estadual Paulista (Unesp)Ribeirão Preto University (UNAERP)Cardoso, Laís Medeiros [UNESP]Pansani, Taisa Nogueira [UNESP]Hebling, Josimeri [UNESP]de Souza Costa, Carlos Alberto [UNESP]Basso, Fernanda Gonçalves2021-06-25T11:00:34Z2021-06-25T11:00:34Z2021-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.archoralbio.2021.105159Archives of Oral Biology, v. 127.1879-15060003-9969http://hdl.handle.net/11449/20776110.1016/j.archoralbio.2021.1051592-s2.0-85106323886Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengArchives of Oral Biologyinfo:eu-repo/semantics/openAccess2024-09-27T14:57:34Zoai:repositorio.unesp.br:11449/207761Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-27T14:57:34Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells |
title |
Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells |
spellingShingle |
Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells Cardoso, Laís Medeiros [UNESP] Chemotherapy Cytokines Fibroblasts Keratinocytes Matrix metalloproteinases Oral mucositis |
title_short |
Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells |
title_full |
Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells |
title_fullStr |
Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells |
title_full_unstemmed |
Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells |
title_sort |
Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells |
author |
Cardoso, Laís Medeiros [UNESP] |
author_facet |
Cardoso, Laís Medeiros [UNESP] Pansani, Taisa Nogueira [UNESP] Hebling, Josimeri [UNESP] de Souza Costa, Carlos Alberto [UNESP] Basso, Fernanda Gonçalves |
author_role |
author |
author2 |
Pansani, Taisa Nogueira [UNESP] Hebling, Josimeri [UNESP] de Souza Costa, Carlos Alberto [UNESP] Basso, Fernanda Gonçalves |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Ribeirão Preto University (UNAERP) |
dc.contributor.author.fl_str_mv |
Cardoso, Laís Medeiros [UNESP] Pansani, Taisa Nogueira [UNESP] Hebling, Josimeri [UNESP] de Souza Costa, Carlos Alberto [UNESP] Basso, Fernanda Gonçalves |
dc.subject.por.fl_str_mv |
Chemotherapy Cytokines Fibroblasts Keratinocytes Matrix metalloproteinases Oral mucositis |
topic |
Chemotherapy Cytokines Fibroblasts Keratinocytes Matrix metalloproteinases Oral mucositis |
description |
Objective: Oral mucositis (OM), the most common side effect of cancer therapy, is associated with pro-inflammatory cytokines and matrix metalloproteinases (MMPs) increased expression. Although there are approaches for OM management, none is infallible, thus, elucidation of molecular events related to OM etiopathogenesis may improve current therapeutic strategies. This study assessed the influence of pro-inflammatory cytokines and chemotherapy drugs on MMPs expression and synthesis by oral mucosa cells. Design: Human gingival fibroblasts (HGF) were exposed to different concentrations of methotrexate (MTX) and 5-fluorouracil (5-FU); subsequentially, cell viability, nitric oxide and interleukin(IL)-6 production were evaluated to select the concentration of these drugs that could stimulate inflammatory phenotype without cytotoxic effects. Then, HGF and primary gingival keratinocytes (PGK) were subjected to different stimuli: culture medium (negative control), tumor necrosis factor-alpha (TNF-α – positive control), IL-6, IL-8, MTX, and 5-FU for 3, 6, 12, and 24 h. Next, gene expression and synthesis of MMP-2 and MMP-9 by HGF and MMP-3 by PGK were assessed. Results: At 6 h, MMP-2 synthesis increased 60 % after exposure to TNF-α and MTX, 40 % after IL-6, and 15 % after IL-8. At 12 h, MMP-9 synthesis increased 15 % after exposure to TNF-α, while MMP-3 synthesis increased 30 % after TNF-α, and 10 % after IL-8. TNF-α-treated groups presented increased gene expression of all MMPs evaluated. IL-8 and 5-FU increased MMP-2 and MMP-3 expression, while IL-6 and MTX augmented MMP-2 expression. Conclusions: The chemotherapy drugs and cytokines investigated up-regulated MMPs expression by oral mucosa cells, which may lead to OM establishment and severity. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T11:00:34Z 2021-06-25T11:00:34Z 2021-07-01 |
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://dx.doi.org/10.1016/j.archoralbio.2021.105159 Archives of Oral Biology, v. 127. 1879-1506 0003-9969 http://hdl.handle.net/11449/207761 10.1016/j.archoralbio.2021.105159 2-s2.0-85106323886 |
url |
http://dx.doi.org/10.1016/j.archoralbio.2021.105159 http://hdl.handle.net/11449/207761 |
identifier_str_mv |
Archives of Oral Biology, v. 127. 1879-1506 0003-9969 10.1016/j.archoralbio.2021.105159 2-s2.0-85106323886 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Archives of Oral Biology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus 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 |
repositoriounesp@unesp.br |
_version_ |
1813546535291453440 |