LPS-induced iNOS expression in N9 microglial cells is suppressed by geniposide via ERK, p38 and nuclear factor-κB signaling pathways

Zhang,Gu; He,Jun-Lin; Xie,Xiao-Yan; Yu,Chao

doi:10.3892/ijmm.2012.1030

September 2012 Volume 30 Issue 3

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September 2012 Volume 30 Issue 3

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Article

LPS-induced iNOS expression in N9 microglial cells is suppressed by geniposide via ERK, p38 and nuclear factor-κB signaling pathways

Authors:
- Gu Zhang
- Jun-Lin He
- Xiao-Yan Xie
- Chao Yu
View Affiliations / Copyright

Affiliations: Department of Pathology, Zhejiang Cancer Hospital, Zhejiang 310022, P.R. China, Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, P.R. China, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, P.R. China
Pages: 561-568
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Published online on: June 14, 2012

https://doi.org/10.3892/ijmm.2012.1030
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Abstract

Activated microglia producing reactive nitrogen species, inflammatory factors, reactive oxygen species (ROS) and other neurovirulent factors, can lead to the development of neurodegenerative diseases. Certain compounds can inhibit the activation of microglia. However, the mechanisms remain unclear. In the present study, we investigated the inhibitory effect of geniposide on the production of ROS and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated N9 murine microglial cells through the p38, ERK1/2 and nuclear factor-κB (NF-κB) signaling pathways. After the N9 cells were pre-treated with the vehicle or geniposide and exposed to LPS for the time indicated, the MTT conversion test was used to assess cell viability. Suitable concentrations were chosen and adjusted according to the experiments. Extracellular nitric oxide (NO) release was measured by Griess reaction. The formation of ROS and intracellular NO was evaluated by fluorescence imaging. NOS activities were determined using commercially available kits. The morphology of the N9 cells was examined by hematoxylin and eosin staining. The expression of iNOS mRNA was examined by RT-PCR. The protein levels of iNOS, p38 mitogen-activated protein kinase (MAPK), ERK1/2 and NF-κB, inhibitory factor-κB-α (IκB-α) were determined by western blot analysis. The results showed that geniposide attenuated the activation of N9 cells and inhibited the overproduction of NO, intracellular ROS and the expression of iNOS induced by LPS in the cells. In addition, geniposide blocked the phosphorylation of p38, ERK1/2 and inhibited the drop-off of IκB induced by LPS in the cells. These data indicate that geniposide has therapeutic potential for the treatment of neurodegenerative diseases, and that it exerts its effects by inhibiting inflammation.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

LPS-induced iNOS expression in N9 microglial cells is suppressed by geniposide via ERK, p38 and nuclear factor-κB signaling pathways

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