Universita degli Studi di Genova, DIMI and IRCCS AOU San Martino IST, Genova, Italy.
J Nephrol. 2017 Dec;30(6):719-727. doi: 10.1007/s40620-017-0432-8. Epub 2017 Sep 20.
Toll-like receptors (TLRs) are a class of receptors of the innate immune system which detect pathogen-associated and danger-associated molecular patterns in order to initiate an inflammatory response. TLR2 and TLR4 downward signaling causes the production of proinflammatory cytokines that can induce insulin resistance and cardiovascular damage in obesity and type 2 diabetes mellitus. In diabetic nephropathy, TLR4, nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and NLRP3 inflammasome are involved in the production and persistence of inflammation. The activation of TLRs stimulates the expression of several inflammatory cytokines and chemokines such as CCL2 and tumor necrosis factor (TNF)-α, which are associated with the progression of diabetic nephropathy. Different inflammatory mechanisms seem to take place in the early and late stages of diabetic kidney disease, with activation of the innate immunity response and enhanced chemiotactic effects in native kidney cells at an early stage, followed by tubulointerstitial monocyte infiltration at a more advanced disease state. Overall, available data indicate that the upregulated TLR4 response in the kidney translates the metabolic alterations of diabetes into kidney damage.
Toll 样受体 (TLRs) 是先天免疫系统的一类受体，可识别病原体相关和危险相关的分子模式，从而引发炎症反应。TLR2 和 TLR4 的向下信号传导导致促炎细胞因子的产生，这可能导致肥胖和 2 型糖尿病中的胰岛素抵抗和心血管损伤。在糖尿病肾病中，TLR4、核苷酸结合寡聚化结构域包含蛋白 2 (NOD2) 和 NLRP3 炎性小体参与炎症的产生和持续。TLRs 的激活刺激几种炎症细胞因子和趋化因子的表达，如 CCL2 和肿瘤坏死因子 (TNF)-α，这些与糖尿病肾病的进展有关。不同的炎症机制似乎在糖尿病肾病的早期和晚期发生，在早期阶段，先天免疫反应的激活和对固有肾脏细胞的趋化作用增强，随后在更晚期的疾病状态下出现肾小管间质单核细胞浸润。总的来说，现有数据表明，肾脏中 TLR4 反应的上调将糖尿病的代谢改变转化为肾脏损伤。
