Details

Autor(en) / Beteiligte

• Sun, Junran
• Huang, Peirong
• Liang, Jian
• Li, Jie
• Shen, Mengxi
• She, Xiangjun
• Feng, Yiji
• Luo, Xueting
• Liu, Te
• Sun, Xiaodong

Titel

Cooperation of Rel family members in regulating Aβ1-40-mediated pro-inflammatory cytokine secretion by retinal pigment epithelial cells

Ist Teil von

• Cell death & disease, 2017-10, Vol.8 (10), p.e3115-e3115

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2017

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Amyloid-beta (A β ) is a hallmark component of age-related macular degeneration (AMD), which induces secretion of pro-inflammatory cytokines from retinal pigment epithelium (RPE). Previous studies have shown that p50/RelA (p65), a member of NF- κ B family, is an essential pro-inflammatory transcription factor responding to A β 1-40 stimulation, but few focused on the other two Rel transcription factor members – RelB and c-Rel – and their role in A β 1-40 -mediated inflammation. It was reported that RelA, RelB and c-Rel are also implicated in various NF- κ B-mediated inflammatory diseases. Therefore, we infer that A β 1-40 -mediated inflammation targets not only the classical inflammation regulator, RelA, but also RelB and c-Rel. In this study, we demonstrate that intravitreally injected A β 1-40 mice develop AMD-like pathologic changes, coupled with Rel protein (RelA, RelB and c-Rel) synthesis and nuclear translocation. To focus on the interaction mechanism of Rel proteins, we found that RelB and c-Rel formed a heterodimer with RelA in mice model. We also found that c-Rel silencing decreased the levels of A β 1-40 -dependent RelA expression, indicating that RelB and c-Rel may interact with RelA as coactivator and c-Rel is required to activate the expression of RelA. Moreover, Rel protein silencing decreased the expression of distinct pro-inflammatory cytokines. Together, we demonstrate that besides RelA, RelB and c-Rel can also be activated by A β 1-40 , all of which mediate pro-inflammatory cytokine transcription and RPE damage. Our findings imply that RPE-mediated inflammation under the stimulation of A β 1-40 is multi-targeted and RelA, RelB and c-Rel proteins may be the new targets of anti-inflammatory agents.