Etanercept restores normal insulin signal transduction in β2-adrenergic receptor knockout mice

Journal of Neuroinflammation

Jena J Steinle²  Eun-Ah Ye¹  Qiuhua Zhang¹  Youde Jiang¹ 

[1] Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN, USA;Department of Ophthalmology, Hamilton Eye Institute, 930 Madison Ave, Suite 768A, Memphis 38163, TN, USA

关键词: Insulin signaling;    Apoptosis;    SOCS3;    TNFα;   

Others  :  1151074
DOI  :  10.1186/s12974-014-0137-z

 received in 2014-06-19, accepted in 2014-07-27,  发布年份 2014

【 摘 要 】

Background

Inhibition of TNFα protects the retina against diabetic-like changes in rodent models. The mechanism by which TNFα induces deleterious retinal changes is not known. Previously, we have shown that TNFα can inhibit normal insulin signal transduction, leading to increased apoptosis in both retinal endothelial cells (REC) and Müller cells. Additionally, β2-adrenergic receptor knockout mice (β2KO) have increased TNFα levels and decreased insulin receptor activity. In this study, we hypothesized that inhibition of TNFα in β2KO mice would increase normal insulin signaling, leading to improved retinal function.

Methods

C57BL6 or β2KO mice were left untreated or treated with etanercept (0.3 mg/kg subcutaneously, 3× a week) for 2 months. Electroretinogram analyses were done before treatment was initiated and after two months of treatment with etanercept on all mice. Western blot or ELISA analyses were done on whole retinal lysates from all four groups of mice for TNFα, suppressor of cytokine signaling 3 (SOCS3), insulin receptor, and apoptotic proteins.

Results

Etanercept significantly reduced TNFα levels in β2KO mice, leading to increased insulin receptor phosphorylation on tyrosine 1150/1151. SOCS3 levels were increased in β2KO mice, which were reduced after etanercept treatment. Pro-apoptotic proteins were reduced in etanercept-treated β2KO mice. Etanercept improved ERG amplitudes in β2KO mice.

Conclusions

Inhibition of TNFα by etanercept protects the retina likely through reduced TNFα-mediated insulin resistance, leading to reduced apoptosis.

【 授权许可】

   
2014 Jiang et al.

【 图 表 】

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