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氧化应激产物羧乙基吡咯增强巨噬细胞中TLR2/TLR1炎症信号传导。

The oxidative stress product carboxyethylpyrrole potentiates TLR2/TLR1 inflammatory signaling in macrophages.

作者信息

Saeed Ali M, Duffort Stephanie, Ivanov Dmitry, Wang Hua, Laird James M, Salomon Robert G, Cruz-Guilloty Fernando, Perez Victor L

机构信息

Sheila and David Fuente Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.

出版信息

PLoS One. 2014 Sep 3;9(9):e106421. doi: 10.1371/journal.pone.0106421. eCollection 2014.

DOI:10.1371/journal.pone.0106421
PMID:25184331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4153630/
Abstract

Oxidative stress is key in the pathogenesis of several diseases including age-related macular degeneration (AMD), atherosclerosis, diabetes, and Alzheimer's disease. It has previously been established that a lipid peroxidation product, carboxyethylpyrrole (CEP), accumulates in the retinas of AMD patients. Retinal infiltrating macrophages also accumulate in the retinas of both AMD patients and in a murine model of AMD. We therefore investigated the ability of CEP-adducts to activate innate immune signaling in murine bone-marrow derived macrophages (BMDMs). We found that CEP specifically synergizes with low-dose TLR2-agonists (but not agonists for other TLRs) to induce production of inflammatory cytokines. Moreover, CEP selectively augments TLR2/TLR1-signaling instead of TLR2/TLR6-signaling. These studies uncover a novel synergistic inflammatory relationship between an endogenously produced oxidation molecule and a pathogen-derived product, which may have implications in the AMD disease process and other oxidative stress-driven pathologies.

摘要

氧化应激在包括年龄相关性黄斑变性（AMD）、动脉粥样硬化、糖尿病和阿尔茨海默病在内的多种疾病的发病机制中起着关键作用。此前已经证实，一种脂质过氧化产物羧乙基吡咯（CEP）在AMD患者的视网膜中积累。视网膜浸润巨噬细胞也在AMD患者的视网膜以及AMD小鼠模型的视网膜中积累。因此，我们研究了CEP加合物激活小鼠骨髓来源巨噬细胞（BMDM）中固有免疫信号的能力。我们发现，CEP与低剂量TLR2激动剂（而非其他TLR的激动剂）特异性协同作用，以诱导炎性细胞因子的产生。此外，CEP选择性增强TLR2/TLR1信号传导而非TLR2/TLR6信号传导。这些研究揭示了内源性产生的氧化分子与病原体衍生产物之间一种新的协同炎症关系，这可能对AMD疾病进程及其他氧化应激驱动的病理状况具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/4787c1c922be/pone.0106421.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/13b5b90e3eba/pone.0106421.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/216d589d4209/pone.0106421.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/dfdd295aaae3/pone.0106421.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/5eb0c4c499c1/pone.0106421.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/6cec33fc4f38/pone.0106421.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/534d818f3365/pone.0106421.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/4787c1c922be/pone.0106421.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/13b5b90e3eba/pone.0106421.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/216d589d4209/pone.0106421.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/dfdd295aaae3/pone.0106421.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/5eb0c4c499c1/pone.0106421.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/6cec33fc4f38/pone.0106421.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/534d818f3365/pone.0106421.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd46/4153630/4787c1c922be/pone.0106421.g007.jpg

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