目的测定脓毒症患儿白介素1受体1(IL-1R1)、活性蛋白C(APC)、降钙素原(PCT)表达水平,探讨其判断脓毒症严重程度的临床价值。方法选取2015年河北省儿童医院重症监护室收治的脓毒症患儿66例,根据诊断标准,其中脓毒症38例(脓毒症组),严重...目的测定脓毒症患儿白介素1受体1(IL-1R1)、活性蛋白C(APC)、降钙素原(PCT)表达水平,探讨其判断脓毒症严重程度的临床价值。方法选取2015年河北省儿童医院重症监护室收治的脓毒症患儿66例,根据诊断标准,其中脓毒症38例(脓毒症组),严重脓毒症28例(严重脓毒症组)。另选取同期体检健康儿童30例作为对照组。检测比较脓毒症组及严重脓毒症组入院24 h时、对照组体检时血清IL-1R1、APC、PCT表达水平;并采用受试者工作特征(ROC)曲线评价入院24 h时IL-1R1、APC、PCT判断脓毒症严重程度的价值。结果 3组入院24 h时IL-1R1、APC、PCT表达水平比较,差异均有统计学意义(P<0.05);其中脓毒症组IL-1R1、PCT水平高于对照组,APC水平低于对照组;严重脓毒症组IL-1R1水平高于对照组,APC水平低于对照组,高于脓毒症组,PCT水平高于对照组和脓毒症组(P<0.05)。入院24 h IL-1R1判断脓毒症患儿发生严重脓毒症的ROC曲线下面积(AUC)为0.597,与AUC=0.500比较,差异无统计学意义(P=0.198);入院24 h APC判断脓毒症患儿发生严重脓毒症的AUC为0.686,与AUC=0.500比较,差异有统计学意义(P=0.013);入院24 h PCT判断脓毒症患儿发生严重脓毒症的AUC为0.817,与AUC=0.500比较,差异有统计学意义(P<0.001)。入院24 h三者联合判断脓毒症患儿发生严重脓毒症的AUC为0.834,与AUC=0.500比较,差异有统计学意义(P<0.001)。结论脓毒症及严重脓毒症患儿血清IL-1R1、PCT、APC水平较正常儿童存在差异。PCT及三者联合判断脓毒症严重程度的价值较高,可以作为判断病情的参考指标。展开更多
Interleukin-1β(IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity.The assembly of the receptor complex,consisting of the ligand IL-1β,the IL-1 receptor(IL-1R)type...Interleukin-1β(IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity.The assembly of the receptor complex,consisting of the ligand IL-1β,the IL-1 receptor(IL-1R)type 1(IL1R1),and the IL-1R accessory protein(IL1RAP),initiates this signaling.However,how the IL1R1-associated complex is regulated remains elusive.Angiopoietin like 3(ANGPTL3),a key inhibitor of plasma triglyceride clearance,is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms.Currently,ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases.However,most studies have focused on the secreted form of ANGPTL3,while its intracellular role is still largely unknown.Here,we report that intracellular ANGPTL3 acts as a negative regulator of IL-1β-triggered signaling.Overexpression of ANGPTL3 inhibited IL-1β-induced NF-κB activation and the transcription of inflammatory genes in HepG2,THP1,and HEK293T cells,while knockdown or knockout of ANGPTL3 resulted in opposite effects.Mechanistically,ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain and disrupted the assembly of the IL1R1-associated complex.Taken together,our study reveals a novel role for ANGPTL3 in inflammation,whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.展开更多
文摘目的测定脓毒症患儿白介素1受体1(IL-1R1)、活性蛋白C(APC)、降钙素原(PCT)表达水平,探讨其判断脓毒症严重程度的临床价值。方法选取2015年河北省儿童医院重症监护室收治的脓毒症患儿66例,根据诊断标准,其中脓毒症38例(脓毒症组),严重脓毒症28例(严重脓毒症组)。另选取同期体检健康儿童30例作为对照组。检测比较脓毒症组及严重脓毒症组入院24 h时、对照组体检时血清IL-1R1、APC、PCT表达水平;并采用受试者工作特征(ROC)曲线评价入院24 h时IL-1R1、APC、PCT判断脓毒症严重程度的价值。结果 3组入院24 h时IL-1R1、APC、PCT表达水平比较,差异均有统计学意义(P<0.05);其中脓毒症组IL-1R1、PCT水平高于对照组,APC水平低于对照组;严重脓毒症组IL-1R1水平高于对照组,APC水平低于对照组,高于脓毒症组,PCT水平高于对照组和脓毒症组(P<0.05)。入院24 h IL-1R1判断脓毒症患儿发生严重脓毒症的ROC曲线下面积(AUC)为0.597,与AUC=0.500比较,差异无统计学意义(P=0.198);入院24 h APC判断脓毒症患儿发生严重脓毒症的AUC为0.686,与AUC=0.500比较,差异有统计学意义(P=0.013);入院24 h PCT判断脓毒症患儿发生严重脓毒症的AUC为0.817,与AUC=0.500比较,差异有统计学意义(P<0.001)。入院24 h三者联合判断脓毒症患儿发生严重脓毒症的AUC为0.834,与AUC=0.500比较,差异有统计学意义(P<0.001)。结论脓毒症及严重脓毒症患儿血清IL-1R1、PCT、APC水平较正常儿童存在差异。PCT及三者联合判断脓毒症严重程度的价值较高,可以作为判断病情的参考指标。
基金supported by the Natural Science Foundation of China(31871411,31971066,and 82273838)the National Key R&D Program of China(2022YFA0806100)+1 种基金the Natural Science Foundation of Hubei Province(2021CFA004)the Analytical and Testing Center of Huazhong University of Science and Technology.
文摘Interleukin-1β(IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity.The assembly of the receptor complex,consisting of the ligand IL-1β,the IL-1 receptor(IL-1R)type 1(IL1R1),and the IL-1R accessory protein(IL1RAP),initiates this signaling.However,how the IL1R1-associated complex is regulated remains elusive.Angiopoietin like 3(ANGPTL3),a key inhibitor of plasma triglyceride clearance,is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms.Currently,ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases.However,most studies have focused on the secreted form of ANGPTL3,while its intracellular role is still largely unknown.Here,we report that intracellular ANGPTL3 acts as a negative regulator of IL-1β-triggered signaling.Overexpression of ANGPTL3 inhibited IL-1β-induced NF-κB activation and the transcription of inflammatory genes in HepG2,THP1,and HEK293T cells,while knockdown or knockout of ANGPTL3 resulted in opposite effects.Mechanistically,ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain and disrupted the assembly of the IL1R1-associated complex.Taken together,our study reveals a novel role for ANGPTL3 in inflammation,whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.