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17β-Estradiol Protects the Retinal Nerve Cells Suppressing TLR2 Mediated Immune-Inflammation and Apoptosis from Oxidative Stress Insult Independent of PI3K

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Abstract

The excessive apoptosis of retinal nerve cells (RNCs) could cause a variety of retinal neurodegenerative diseases which could result in the irreversible blindness. In this study, the experiment models of H2O2 and light-induced oxidative insult in the retina of Sprague-Dawley (SD) rat were used. We demonstrated the role of toll-like receptor 2 (TLR2) in apoptosis and immune-inflammation induced by oxidative stress insult. Meanwhile, we also tried to elucidate the modulating mechanism of 17β-estradiol (E2) resistant to TLR2 induced by oxidative stress insult. The cell apoptosis induced by oxidative stress was examined by annexin V-FITC/propidium iodide (PI) assay using flow cytometry and the expressions of TLR2 and inflammatory cytokines were determined by real-time PCR and western blotting. Peptidoglycan (PGN) as the ligand of TLR2 and small interfering RNAs of TLR2 (siTLR2) were used to determine the role of TLR2. From the results, firstly, we demonstrated that E2 could reduce the expressions of TLR2 and inflammatory cytokines including TNF-ɑ, IFN-γ, and IL-1β induced by oxidative stress; secondly, the phosphoinositide 3-kinase (PI3K) could not influence the effect of E2 on reducing TLR2 expression induced by H2O2 in RNCs; thirdly, PGN could promote the damage effect of H2O2 by transforming RNCs from late apoptosis to necrosis, however, E2 could decrease the cell apoptosis mediated by PGN; and finally, the apoptosis of RNCs and the expressions of the inflammatory cytokines induced by H2O2 administration were significantly inhibited after TLR2 interference. In summary, E2 reduces the TLR2-mediated immune-inflammation, thereby protecting RNCs against oxidative stress-induced apoptosis via a PI3K-independent signaling pathway. The present results provide evidence that inhibiting of TLR2-mediated immune-inflammation might be a possible therapeutic way to exert auxiliary role on E2 neuroprotection.

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Abbreviations

E2:

17β-Estradiol

RNCs:

Retinal nerve cells

SD:

Sprague-Dawley

TLRs:

Toll-like receptors

siTLR2:

Small RNA interference of TLR2

PI3K:

Phosphoinositide 3-kinase (PI3K)

LY:

LY294002

PGN:

Peptidoglycan

OS:

Outer segment

IS:

Inner segment

ONL:

Outer nuclear layer

INL:

Inner nuclear layer

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Nos. 81271013 and 81501067) and the Scientific Research Program Funded by Shaanxi Provincial Education Department (No. 14JK1613) and Xi’an Medical University (No. 2015DOC06).

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Authors and Affiliations

  1. The Department of Biochemistry and Molecular Biology, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, 710061, China

    Hongbo Li, Chunhui Zhu, Baoying Wang, Wenhua Zhu, Yan Feng, Fangying Du, Shaolan Wang, Chenghu Hu, Jie Ma & Xiaorui Yu

  2. The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Medical University, Xi’an, Shaanxi, 710021, China

    Hongbo Li

  3. The Department of Biochemistry and Molecular Biology, The Environment and Genes Related to Diseases Key Laboratory of Education Ministry, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, 710061, China

    Xiaorui Yu

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  1. Hongbo Li
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  2. Chunhui Zhu
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  3. Baoying Wang
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Correspondence to Xiaorui Yu.

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Li, H., Zhu, C., Wang, B. et al. 17β-Estradiol Protects the Retinal Nerve Cells Suppressing TLR2 Mediated Immune-Inflammation and Apoptosis from Oxidative Stress Insult Independent of PI3K. J Mol Neurosci 60, 195–204 (2016). https://doi.org/10.1007/s12031-016-0794-8

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  • DOI: https://doi.org/10.1007/s12031-016-0794-8

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