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Crocin Upregulates CX3CR1 Expression by Suppressing NF-κB/YY1 Signaling and Inhibiting Lipopolysaccharide-Induced Microglial Activation

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Abstract

Glaucoma is a group of neurodegenerative diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Microglial activation has been shown to be deleterious to RGCs and may participate in the progression of glaucoma. Crocin, one of the major active ingredients in saffron, has been found to inhibit microglial activation. However, the mechanism remains unclear. The aim of this study was to investigate whether crocin can inhibit lipopolysaccharide (LPS)-induced microglial activation and to clarify the mechanisms involved. The influence of crocin on primary RGCs and LPS-stimulated BV2 microglial cells survival was determined by the MTT and lactate dehydrogenase assays, or by flow cytometry. BV2 cells were pretreated with various concentrations of crocin for 2 h followed by 1 μg/mL LPS stimulation. Microglial markers and pro-inflammatory mediators were assessed by real-time PCR, western blot and ELISA. Furthermore, CX3CR1 expression was detected and the underlying mechanism was examined. The concentrations of crocin ranged from 0.1 to 1 μM, and did not show any cytotoxicity in RGC and BV2 cells. After crocin pretreatment, the expression of microglial markers (CD11b and Iba-1) and pro-inflammatory mediators (iNOS, COX-2, IL-1β, and TNF-α) induced by LPS were significantly decreased in a dose-dependent manner. Additionally, CX3CR1 expression was remarkably increased by crocin via the suppression of NF-κB/Yin Yang 1 (YY1) signaling in BV2 cells. In conclusion, crocin effectively suppresses microglial activation and upregulates CX3CR1 expression by suppressing NF-κB/YY1 signaling.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81273902).

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Authors and Affiliations

  1. Shaanxi Ophthalmic Medical Center, Xi’an No. 4 Hospital, Affiliated Guangren Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China

    Bochang Lv, Zhongqiao Zhu, Zhiguo Xu, Xiaojie Dang & Xinguang Yang

  2. Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an Jiaotong University School of Medicine, Xi’an, 710061, People’s Republic of China

    Fuquan Huo

  3. Department of Anatomy, Histology and Embryology and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

    Tao Chen & Ting Zhang

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  1. Bochang Lv
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Correspondence to Xinguang Yang.

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Lv, B., Huo, F., Zhu, Z. et al. Crocin Upregulates CX3CR1 Expression by Suppressing NF-κB/YY1 Signaling and Inhibiting Lipopolysaccharide-Induced Microglial Activation. Neurochem Res 41, 1949–1957 (2016). https://doi.org/10.1007/s11064-016-1905-1

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  • DOI: https://doi.org/10.1007/s11064-016-1905-1

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