Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways
Patricia Neacsu,1 Anca Mazare,2 Patrik Schmuki,2 Anisoara Cimpean11Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania; 2Department of Materials Science, University of Erlangen-Nuremberg, Erlangen, GermanyAbstract: Biomaterial implantation in a living tissue...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2015
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/5439edd3b23f4bb1918355426776f617 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:5439edd3b23f4bb1918355426776f617 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:5439edd3b23f4bb1918355426776f6172021-12-02T05:51:06ZAttenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways1178-2013https://doaj.org/article/5439edd3b23f4bb1918355426776f6172015-10-01T00:00:00Zhttps://www.dovepress.com/attenuation-of-the-macrophage-inflammatory-activity-by-tio2-nanotubes--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Patricia Neacsu,1 Anca Mazare,2 Patrik Schmuki,2 Anisoara Cimpean11Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania; 2Department of Materials Science, University of Erlangen-Nuremberg, Erlangen, GermanyAbstract: Biomaterial implantation in a living tissue triggers the activation of macrophages in inflammatory events, promoting the transcription of pro-inflammatory mediator genes. The initiation of macrophage inflammatory processes is mainly regulated by signaling proteins of mitogen-activated protein kinase (MAPK) and by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. We have previously shown that titania nanotubes modified Ti surfaces (Ti/TiO2) mitigate the immune response, compared with flat Ti surfaces; however, little is known regarding the underlying mechanism. Therefore, the aim of this study is to investigate the mechanism(s) by which this nanotopography attenuates the inflammatory activity of macrophages. Thus, we analyzed the effects of TiO2 nanotubes on the activation of MAPK and NF-κB signaling pathways in standard and lipopolysaccharide-evoked conditions. Results showed that the Ti/TiO2 significantly reduce the expression levels of the phosphorylated forms of p38, ERK1/2, c-Jun NH2-terminal kinase (JNK), IKKβ, and IkB-α. Furthermore, a significant reduction in the p65 nuclear accumulation on the nanotubular surface was remarked. Following, by using specific MAPK inhibitors, we observed that lipopolysaccharide-induced production of monocyte chemotactic protein-1 and nitric oxide was significantly inhibited on the Ti/TiO2 surface via p38 and ERK1/2, but not via JNK. However, the selective inhibitor for JNK signaling pathway (SP600125) was effective in reducing tumor necrosis factor alpha release as well as monocyte chemotactic protein-1 and nitric oxide production. Altogether, these data suggest that titania nanotubes can attenuate the macrophage inflammatory response via suppression of MAPK and NF-κB pathways providing a potential mechanism for their anti-inflammatory activity.Keywords: titania nanotubes, macrophage, mitogen-activated protein kinases, NF-κB, inflammatory mediatorsNeacsu PMazare ASchmuki PCimpean ADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6455-6467 (2015) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine (General) R5-920 |
| spellingShingle |
Medicine (General) R5-920 Neacsu P Mazare A Schmuki P Cimpean A Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways |
| description |
Patricia Neacsu,1 Anca Mazare,2 Patrik Schmuki,2 Anisoara Cimpean11Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania; 2Department of Materials Science, University of Erlangen-Nuremberg, Erlangen, GermanyAbstract: Biomaterial implantation in a living tissue triggers the activation of macrophages in inflammatory events, promoting the transcription of pro-inflammatory mediator genes. The initiation of macrophage inflammatory processes is mainly regulated by signaling proteins of mitogen-activated protein kinase (MAPK) and by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. We have previously shown that titania nanotubes modified Ti surfaces (Ti/TiO2) mitigate the immune response, compared with flat Ti surfaces; however, little is known regarding the underlying mechanism. Therefore, the aim of this study is to investigate the mechanism(s) by which this nanotopography attenuates the inflammatory activity of macrophages. Thus, we analyzed the effects of TiO2 nanotubes on the activation of MAPK and NF-κB signaling pathways in standard and lipopolysaccharide-evoked conditions. Results showed that the Ti/TiO2 significantly reduce the expression levels of the phosphorylated forms of p38, ERK1/2, c-Jun NH2-terminal kinase (JNK), IKKβ, and IkB-α. Furthermore, a significant reduction in the p65 nuclear accumulation on the nanotubular surface was remarked. Following, by using specific MAPK inhibitors, we observed that lipopolysaccharide-induced production of monocyte chemotactic protein-1 and nitric oxide was significantly inhibited on the Ti/TiO2 surface via p38 and ERK1/2, but not via JNK. However, the selective inhibitor for JNK signaling pathway (SP600125) was effective in reducing tumor necrosis factor alpha release as well as monocyte chemotactic protein-1 and nitric oxide production. Altogether, these data suggest that titania nanotubes can attenuate the macrophage inflammatory response via suppression of MAPK and NF-κB pathways providing a potential mechanism for their anti-inflammatory activity.Keywords: titania nanotubes, macrophage, mitogen-activated protein kinases, NF-κB, inflammatory mediators |
| format |
article |
| author |
Neacsu P Mazare A Schmuki P Cimpean A |
| author_facet |
Neacsu P Mazare A Schmuki P Cimpean A |
| author_sort |
Neacsu P |
| title |
Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways |
| title_short |
Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways |
| title_full |
Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways |
| title_fullStr |
Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways |
| title_full_unstemmed |
Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways |
| title_sort |
attenuation of the macrophage inflammatory activity by tio2 nanotubes via inhibition of mapk and nf-κb pathways |
| publisher |
Dove Medical Press |
| publishDate |
2015 |
| url |
https://doaj.org/article/5439edd3b23f4bb1918355426776f617 |
| work_keys_str_mv |
AT neacsup attenuationofthemacrophageinflammatoryactivitybytio2nanotubesviainhibitionofmapkandnfkappabpathways AT mazarea attenuationofthemacrophageinflammatoryactivitybytio2nanotubesviainhibitionofmapkandnfkappabpathways AT schmukip attenuationofthemacrophageinflammatoryactivitybytio2nanotubesviainhibitionofmapkandnfkappabpathways AT cimpeana attenuationofthemacrophageinflammatoryactivitybytio2nanotubesviainhibitionofmapkandnfkappabpathways |
| _version_ |
1718400171488837632 |