Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway.
Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway.
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Toll像受体（TLR）自由基周期在慢性炎症中的作用：针对TLR4途径的可能治疗方法。
DOI：
10.1007/s12035-013-8425-7
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发表时间：
2013-08
影响因子：
5.1
通讯作者：
Maes M
中科院分区：
文献类型：
--
作者：
Lucas K;Maes M
Toll样受体4(TLR4)复合体是先天免疫系统的受体，它的激活可能是许多人类疾病的病理生理学基础，包括哮喘、心血管疾病、糖尿病、肥胖、代谢综合征、自身免疫性疾病、神经炎性疾病、精神分裂症、双相情感障碍、自闭症、临床抑郁症、慢性疲劳综合征、酗酒和甲苯吸入。TLRs是一种模式识别受体，可以识别损伤相关的分子模式和病原体相关的分子模式，包括来自革兰氏阴性细菌的脂多糖(LPS)。在这里，我们重点讨论已知的触发TLR4的环境因素，例如臭氧、大气颗粒物、长寿命活性氧中间体、五氯苯酚、电离辐射和甲苯。TLR4通路的激活可能导致慢性炎症、活性氧和氮(ROS/RNS)以及氧化和亚硝化应激的产生，从而导致TLR相关疾病。这意味着改变这些途径的药物或物质可以预防或改善上述疾病。在这里，我们回顾了一些最有希望减轻TLR介导的炎症的药物和药物，例如，旨在中和LPS(合成抗内毒素多肽和重组因子C)和TLR4/MyD88拮抗剂的抗LPS策略，包括厄立特里亚、CYP、EM-163、表没食子儿茶素没食子酸酯、6-shogaol、肉桂提取物、N-乙酰半胱氨酸、褪黑素和分子氢。作者认为，TLR自由基(ROS/RNS)循环的激活是许多“文明”障碍的共同途径，靶向TLR自由基循环可能是治疗许多炎症性疾病的有效方法。
Activation of the Toll-like receptor 4 (TLR4) complex, a receptor of the innate immune system, may underpin the pathophysiology of many human diseases, including asthma, cardiovascular disorder, diabetes, obesity, metabolic syndrome, autoimmune disorders, neuroinflammatory disorders, schizophrenia, bipolar disorder, autism, clinical depression, chronic fatigue syndrome, alcohol abuse, and toluene inhalation. TLRs are pattern recognition receptors that recognize damage-associated molecular patterns and pathogen-associated molecular patterns, including lipopolysaccharide (LPS) from gram-negative bacteria. Here we focus on the environmental factors, which are known to trigger TLR4, e.g., ozone, atmosphere particulate matter, long-lived reactive oxygen intermediate, pentachlorophenol, ionizing radiation, and toluene. Activation of the TLR4 pathways may cause chronic inflammation and increased production of reactive oxygen and nitrogen species (ROS/RNS) and oxidative and nitrosative stress and therefore TLR-related diseases. This implies that drugs or substances that modify these pathways may prevent or improve the abovementioned diseases. Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) and TLR4/MyD88 antagonists, including eritoran, CyP, EM-163, epigallocatechin-3-gallate, 6-shogaol, cinnamon extract, N-acetylcysteine, melatonin, and molecular hydrogen. The authors posit that activation of the TLR radical (ROS/RNS) cycle is a common pathway underpinning many “civilization” disorders and that targeting the TLR radical cycle may be an effective method to treat many inflammatory disorders.
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DOI：
10.3390/s110707219
发表时间：
2011
期刊：
Sensors (Basel, Switzerland)
影响因子：
--
作者：
Chen P;Migita S;Kanehira K;Sonezaki S;Taniguchi A
通讯作者：
Taniguchi A
DOI：
10.1152/ajpregu.00307.2007
发表时间：
2007-09-01
影响因子：
2.8
作者：
Bailey, Michael T.;Engler, Harald;Sheridan, John F.
通讯作者：
Sheridan, John F.
影响因子：
3.8
作者：
Bermudez, E;Mangum, JB;Everitt, JI
通讯作者：
Everitt, JI
影响因子：
2.1
作者：
Dick, CAJ;Brown, DM;Stone, V
通讯作者：
Stone, V
影响因子：
5.1
作者：
Chiu, Wen-Ta;Lin, Yi-Ling;Chen, Ruei-Ming
通讯作者：
Chen, Ruei-Ming