Inflammasome Activation in Retinal Pigment Epithelium from Human Donors with Age-Related Macular Degeneration.
Inflammasome Activation in Retinal Pigment Epithelium from Human Donors with Age-Related Macular Degeneration.
复制标题
视网膜色素上皮细胞中的炎性体激活来自患有视网膜相关黄斑变性的人供体。
作者：
黄斑变性（AMD）是老年人致盲的主要原因，其特征在于视网膜色素上皮（RPE）和光感受器的死亡。与发展AMD相关的风险因素之一是在编码补体因子H（CFH）的基因内发现的单核苷酸多态性（SNP）。作为先天免疫系统的一部分，CFH抑制补体旁路途径激活。称为炎性小体的多蛋白复合物也在先天免疫反应中发挥作用。先前的研究报道炎性小体激活可能有助于AMD病理。在这项研究中，我们使用了来自多个供体的原代成人RPE细胞培养物，有和没有AMD，其基因分型为Y402H CFH风险等位基因。我们在RPE组织和细胞培养物中发现了基础水平的补体和炎性小体相关基因和蛋白。此外，用鱼藤酮、巴弗洛霉素A和ATP处理导致炎性小体活化。总体而言，无论疾病状态或CFH基因型如何，对引发和激活的反应相似。虽然这些数据表明炎症体在RPE中存在并活跃，但我们的结果表明炎症体活化可能不会导致早期AMD病理学。
Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by the death of retinal pigment epithelium (RPE) and photoreceptors. One of the risk factors associated with developing AMD is the single nucleotide polymorphism (SNP) found within the gene encoding complement factor H (CFH). Part of the innate immune system, CFH inhibits alternative complement pathway activation. Multi-protein complexes called inflammasomes also play a role in the innate immune response. Previous studies reported that inflammasome activation may contribute to AMD pathology. In this study, we used primary human adult RPE cell cultures from multiple donors, with and without AMD, that were genotyped for the Y402H CFH risk allele. We found complement and inflammasome-related genes and proteins at basal levels in RPE tissue and cell cultures. Additionally, treatment with rotenone, bafilomycin A, and ATP led to inflammasome activation. Overall, the response to priming and activation was similar, irrespective of disease state or CFH genotype. While these data show that the inflammasome is present and active in RPE, our results suggest that inflammasome activation may not contribute to early AMD pathology.
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影响因子：
3.6
作者：
García-Layana A;Cabrera-López F;García-Arumí J;Arias-Barquet L;Ruiz-Moreno JM
通讯作者：
Ruiz-Moreno JM
影响因子：
11.4
作者：
Ferrington DA;Ebeling MC;Kapphahn RJ;Terluk MR;Fisher CR;Polanco JR;Roehrich H;Leary MM;Geng Z;Dutton JR;Montezuma SR
通讯作者：
Montezuma SR
影响因子：
4.8
作者：
Guha, Sonia;Baltazar, Gabriel C.;Mitchell, Claire H.
通讯作者：
Mitchell, Claire H.
影响因子：
6
作者：
Cerniauskas E;Kurzawa-Akanbi M;Xie L;Hallam D;Moya-Molina M;White K;Steel D;Doherty M;Whitfield P;Al-Aama J;Armstrong L;Kavanagh D;Lambris JD;Korolchuk VI;Harris C;Lako M
通讯作者：
Lako M
影响因子：
4.1
作者：
Cao, Sijia;Wang, Jay Ching Chieh;Matsubara, Joanne A.
通讯作者：
Matsubara, Joanne A.