Hyperglycemia induces Toll-like receptor-2 and -4 expression and activity in human microvascular retinal endothelial cells: implications for diabetic retinopathy.
Hyperglycemia induces Toll-like receptor-2 and -4 expression and activity in human microvascular retinal endothelial cells: implications for diabetic retinopathy.
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DOI：
10.1155/2014/790902
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发表时间：
2014
影响因子：
4.3
通讯作者：
Jialal I
中科院分区：
文献类型：
--
作者：
Rajamani U;Jialal I
糖尿病视网膜病变（DR）在工作年龄的成年人中引起视力损害，高血糖介导的炎症是DR的核心，toll样受体（TLRs）在先天免疫反应和炎症中起关键作用。然而，关于它们在dr中的作用的数据很少，因此，在本研究中，我们检测了TLR2和TLR4 mRNA和蛋白在高血糖人视网膜内皮细胞（HMVRECs）中的表达和活性。分别以高血糖（HG）或正常血糖处理HMVRECs，测量TLR-2、TLR-4、MyD88、IRF3、TRIF mRNA和蛋白水平以及NF-κB p65激活。同时检测IL-8、IL-1β、TNF-α、MCP-1、ICAM-1、VCAM-1以及单核细胞对HMVRECs的粘附。HG （25 mM）显著诱导HMVRECs中TLR2和TLR4 mRNA和蛋白表达。它还增加了MyD88和非MyD88途径、核因子-κB （NF-κB）、生物介质和单核细胞粘附。这种炎症通过TLR-4或TLR-2抑制，以及TLR抑制肽、TLR2和4sirna的双重抑制而减轻。此外，抗氧化处理降低了TLR-2和TLR4的表达和下游炎症标志物。总的来说，我们的新数据表明，高血糖诱导TLR-2和TLR-4激活，下游信号可能通过活性氧（ROS）介导炎症增加，并可能导致DR。
Diabetic retinopathy (DR) causes visual impairment in working age adults and hyperglycemia-mediated inflammation is central in DR. Toll-like receptors (TLRs) play a key role in innate immune responses and inflammation. However, scanty data is available on their role in DR. Hence, in this study, we examined TLR2 and TLR4 mRNA and protein expression and activity in hyperglycemic human retinal endothelial cells (HMVRECs). HMVRECs were treated with hyperglycemia (HG) or euglycemia and mRNA and protein levels of TLR-2, TLR-4, MyD88, IRF3, and TRIF as well as NF-κB p65 activation were measured. IL-8, IL-1β, TNF-α and MCP-1, ICAM-1, and VCAM-1 as well as monocyte adhesion to HMVRECs were also assayed. HG (25 mM) significantly induced TLR2 and TLR4 mRNA and protein in HMVRECs. It also increased both MyD88 and non-MyD88 pathways, nuclear factor-κB (NF-κB), biomediators, and monocyte adhesion. This inflammation was attenuated by TLR-4 or TLR-2 inhibition, and dual inhibition by a TLR inhibitory peptide as well as TLR2 and 4 siRNA. Additionally, antioxidant treatment reduced TLR-2 and TLR4 expression and downstream inflammatory markers. Collectively, our novel data suggest that hyperglycemia induces TLR-2 and TLR-4 activation and downstream signaling mediating increased inflammation possibly via reactive oxygen species (ROS) and could contribute to DR.
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影响因子：
--
作者：
Kern, Timothy S.
通讯作者：
Kern, Timothy S.
影响因子：
16.2
作者：
Jialal I;Huet BA;Kaur H;Chien A;Devaraj S
通讯作者：
Devaraj S
影响因子：
13.7
作者：
Hikichi, T;Fujio, N;Yoshida, A
通讯作者：
Yoshida, A
DOI：
10.1152/ajpendo.00302.2006
发表时间：
2007-03-01
影响因子：
5.1
作者：
Creely, S. J.;McTernan, P. G.;Kumar, S.
通讯作者：
Kumar, S.
影响因子：
4.4
作者：
Kowluru, RA;Abbas, SN
通讯作者：
Abbas, SN