The pro-inflammatory role of high-mobility group box 1 protein (HMGB-1) in photoreceptors and retinal explants exposed to elevated pressure

被引:18
作者
Boehm, Michael R. R. [1 ,2 ]
Schallenberg, Maurice [1 ,3 ]
Brockhaus, Katrin [1 ]
Melkonyan, Harutyun [1 ]
Thanos, Solon [1 ,4 ]
机构
[1] Univ Munster, Sch Med, Inst Expt Ophthalmol, Albert Schweitzer Campus 1,D15, D-48149 Munster, Germany
[2] St Franziskus Hosp Munster, Dept Ophthalmol, Munster, Germany
[3] Univ Hosp Essen, Dept Ophthalmol, Essen, Germany
[4] Cluster Excellence Cells Mot, Munster, Germany
关键词
ISCHEMIA-REPERFUSION INJURY; OCULAR HYPERTENSION; RECEPTOR; 4; T-CELLS; KAPPA-B; APOPTOSIS; CYTOKINE; RELEASE; ACTIVATION; EXPRESSION;
D O I
10.1038/labinvest.2015.156
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
To determine the role of high-mobility group box 1 protein (HMGB-1) in cellular and tissue models of elevated pressure induced neurodegeneration, regeneration, and inflammation. Mouse retinal photoreceptor-derived cells (661W) and retinal explants were incubated either under elevated pressure or in the presence of recombinant HMGB-1 (rHMGB-1) to investigate the mechanisms of response of photoreceptors. Immunohistochemistry, western blotting, and the quantitative real-time PCR were used to examine the expression levels of immunological factors (eg, HMGB-1, receptor for advanced glycation end products (RAGE)), Toll-like receptors 2 and 4 (TLR-2, TLR-4), apoptosis-related factors (eg, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad)) as well as cytokine expression (eg, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-4, IL-6, and vascular endothelial growth factor (VEGF)). The data revealed increased the expression of HMGB-1 and its receptors RAGE, TLR-2, and TLR-4, and TNF-a as well as pro-apoptotic factors (eg, Bad) as well as apoptosis in 661W cells exposed to elevated pressure. Co-cultivation of 661W cells with rHMGB-1 increased the expression levels of pro-apoptotic Bad and cleaved Caspase-3 resulting in apoptosis. Cytokine array studies revealed an increased release of TNF-a, IL-4, IL-6, and VEGF after incubation of 661W cells with rHMGB-1. Upregulation of HMGB-1, TLR-2, and RAGE as well as anti-apoptotic Bcl-2 expression levels was found in the retinal explants exposed to rHMGB-1 or elevated pressure. The results suggest that HMGB-1 promotes an inflammatory response and mediates apoptosis in the pathology of photoreceptors and retinal homeostasis. HMGB-1 may have a key role in ongoing damage of retinal cells under conditions of elevated intraocular pressure.
引用
收藏
页码:409 / 427
页数:19
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