International immunopharmacology · 2016
TLR4 signaling mediates AP-1 activation in an MPTP-induced mouse model of Parkinson's disease.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhao Xu-Dong, Wang Fa-Xiang, Cao Wen-Fu, Zhang Yong-Hong, Li Yan
Аннотация
OBJECTIVE: To evaluate the effects of Toll-like receptor 4 (TLR4) signaling on the activation of the transcription factor activator protein-1 (AP-1) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD).
METHODS: The following groups were evaluated: normal saline (NS)-treated WT mice, NS-treated TLR4-knockout (KO) mice, MPTP-treated WT mice, and MPTP-treated TLR4-KO mice. After establishing the mouse model, behavioral changes were evaluated. AP-1 expression was detected by RT-PCR, Western blotting, immunohistochemistry and immunofluorescence staining.
RESULTS: Compared to MPTP-treated WT mice, significantly reduced dyskinesia was observed in MPTP-treated TLR4-KO mice. AP-1 mRNA and protein levels were significantly up-regulated in the substantia nigras (SNs) of MPTP-treated WT mice relative to NS-treated mice (P<0.01); these levels were significantly reduced in MPTP-treated TLR4-KO mice relative to MPTP-treated WT mice (P<0.01). Immunohistochemical staining demonstrated that AP-1 was distributed throughout the SN in MPTP-treated mice, and immunofluorescence further showed that AP-1 was expressed in TH-positive neuronal cells and GFAP-positive astrocytes. In addition, immunofluorescence revealed that AP-1 expression was lower in TH-positive neurons and GFAP-positive astrocytes in the SNs of MPTP-treated TLR4-KO mice relative to MPTP-treated WT mice.
CONCLUSIONS: The TLR4 pathway may play an important role in regulating AP-1 activation.
METHODS: The following groups were evaluated: normal saline (NS)-treated WT mice, NS-treated TLR4-knockout (KO) mice, MPTP-treated WT mice, and MPTP-treated TLR4-KO mice. After establishing the mouse model, behavioral changes were evaluated. AP-1 expression was detected by RT-PCR, Western blotting, immunohistochemistry and immunofluorescence staining.
RESULTS: Compared to MPTP-treated WT mice, significantly reduced dyskinesia was observed in MPTP-treated TLR4-KO mice. AP-1 mRNA and protein levels were significantly up-regulated in the substantia nigras (SNs) of MPTP-treated WT mice relative to NS-treated mice (P<0.01); these levels were significantly reduced in MPTP-treated TLR4-KO mice relative to MPTP-treated WT mice (P<0.01). Immunohistochemical staining demonstrated that AP-1 was distributed throughout the SN in MPTP-treated mice, and immunofluorescence further showed that AP-1 was expressed in TH-positive neuronal cells and GFAP-positive astrocytes. In addition, immunofluorescence revealed that AP-1 expression was lower in TH-positive neurons and GFAP-positive astrocytes in the SNs of MPTP-treated TLR4-KO mice relative to MPTP-treated WT mice.
CONCLUSIONS: The TLR4 pathway may play an important role in regulating AP-1 activation.