Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of N...Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.展开更多
目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interle...目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-18(interleukin-18,IL-18)在急性脑梗死患者血浆中的表达及意义。方法:纳入急性脑梗死患者85例为脑梗死组,根据神经功能缺损严重程度、脑梗死面积及发病后第90天的改良Rankin量表(Modified Rankin Scale,mRS)评分分为轻、中及重度组,小、中及大面积组,预后良好组及预后不良组。纳入同期健康体检者85例为对照组。采用酶联免疫吸附(enzyme-linked immunosorbnent assay,ELISA)法检测AIM2、IL-1β和IL-18在这两组人群血浆中的表达水平。结果:脑梗死组血浆AIM2、IL-1β和IL-18水平均明显高于对照组,差异均具有统计学意义(均P<0.001)。脑梗死组亚组比较示:患者血浆AIM2、IL-1β和IL-18水平在重度神经功能缺损严重程度组>中度组>轻度组,在大面积脑梗死组>中面积组>小面积组,在预后不良组>预后良好组,差异均具有统计学意义(均P<0.05);血浆AIM2水平与美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑梗死面积及mRS评分呈正相关(分别r=0.791、r=0.710、r=0.763,均P<0.001),IL-1β水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.716、r=0.690、r=0.688,均P<0.001),IL-18水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.714、r=0.638、r=0.653,均P<0.001);血浆AIM2与IL-1β、IL-18水平呈正相关(分别r=0.828、r=0.751,均P<0.001)。结论:AIM2、IL-1β和IL-18在急性脑梗死患者血浆中表达上调,而且与急性脑梗死患者的神经功能缺损严重程度、脑梗死面积及预后密切相关,提示AIM2、IL-1β和IL-18可能在急性脑梗死的发生、发展中起重要作用。展开更多
Inflammasomes are multiprotein intracellular complexes which are responsible for the activation of inflammatory responses. Among various subtypes of inflammasomes, NLRP3 has been a subject of intensive investigation. ...Inflammasomes are multiprotein intracellular complexes which are responsible for the activation of inflammatory responses. Among various subtypes of inflammasomes, NLRP3 has been a subject of intensive investigation. NLRP3 is considered to be a sensor of microbial and other danger signals and plays a crucial role in mucosal immune responses, promoting the maturation of proinflammatory cytokines interleukin 1β(IL-1β) and IL-18. NLRP3 inflammasome has been associated with a variety of inflammatory and autoimmune conditions, including inflammatory bowel diseases(IBD). The role of NLRP3 in IBD is not yet fully elucidated as it seems to demonstrate both pathogenic and protective effects. Studies have shown a relationship between genetic variants and mutations in NLRP3 gene with IBD pathogenesis. A complex interaction between the NLRP3 inflammasome and the mucosal immune response has been reported. Activation of the inflammasome is a key function mediated by the innate immune response and in parallel the signaling through IL-1β and IL-18 is implicated in adaptive immunity. Further research is needed to delineate the precise mechanisms of NLRP3 function in regulating immune responses. Targeting NLRP3 inflammasome and its downstream signaling will provide new insights into the development of future therapeutic strategies.展开更多
目的检测NLRP3炎性小体及其下游炎性因子IL-1β/IL-18在类风湿性关节炎(rheumatoid arthritis,RA)患者滑膜被覆细胞及滑膜间质中的表达及分布情况,探讨NLRP3炎症复合体在RA免疫调节中的作用机制。方法采用免疫组化EnVision法检测30例RA...目的检测NLRP3炎性小体及其下游炎性因子IL-1β/IL-18在类风湿性关节炎(rheumatoid arthritis,RA)患者滑膜被覆细胞及滑膜间质中的表达及分布情况,探讨NLRP3炎症复合体在RA免疫调节中的作用机制。方法采用免疫组化EnVision法检测30例RA、10例骨性关节炎(osteoarthritis,OA)患者滑膜被覆细胞及滑膜间质中NLRP3、Caspase-1及其下游炎性因子IL-1β及IL-18的表达。采用Spearman秩相关分析RA患者滑膜组织中NLRP3炎性小体及其下游炎性因子IL-1β/IL-18的表达水平与RA临床和实验室参数的相关性。结果 NLRP3在RA、OA组中的阳性率分别为100.00%和70.00%,Caspase-1在RA、OA组中的阳性率分别为100.00%和50.00%,IL-1β在RA、OA组中的阳性率分别为100.00%和60.00%,IL-18在RA、OA组中的阳性率分别为86.67%和0,NLRP3、Caspase-1、IL-1β及IL-18在RA和OA组间差异均有统计学意义( P <0.05)。IL-1β与RF表达呈显著正相关( P <0.05);NLRP3与CRP、RF、Caspase-1及IL-1β表达均呈显著正相关( P <0.05),而与IL-18表达无相关性( P >0.05)。结论 NLRP3/Caspase-1信号通路因子在RA的发病过程中起重要作用,且与疾病的活动性密切相关。IL-1β的分泌主要是由Caspase-1介导产生,提示抑制NLRP3或Caspase-1可有效下调IL-1β的表达,可能是RA潜在的治疗靶点,具有重要的临床指导意义。展开更多
AIM： To assess the therapeutic effect of Caspase-1 inhibitors （ICE-I） on acute lung injury （ALI） in experimental severe acute pancreatitis （SAP）. METHODS： Forty-two SD rats were randomly divided into 3 groups...AIM： To assess the therapeutic effect of Caspase-1 inhibitors （ICE-I） on acute lung injury （ALI） in experimental severe acute pancreatitis （SAP）. METHODS： Forty-two SD rats were randomly divided into 3 groups： healthy controls （HC, n = 6）; SAP-S group （n = 18）; SAP-ICE-i group （n = 18）. SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion, in SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum 1L-1β was measured by EUSA. Intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated. RESULTS： Serum IL-1β levels in SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h, which were increased significantly （P 〈 0.01, vs HC）. in SAP- ICE-I group, those values were decreased significantly （P 〈 0.01, vs SAP-S）. intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group （P 〈 0.01, vs HC）. The expression of IL-lβ and IL-18 mRNA were decreased significantly in the SAP- ICE-I group （P 〈 0.01, vs SAP-S）, whereas Caspase-1 mRNA expression had no significant difference （P 〉 0.05）. The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly （P 〈 0.05 at 6 h, P 〈 0.01 at 12 h and 18 h, vs HC） and they were decreased significantly in the SAP-ICE-I group （P 〈 0.05, vs SAP-S）.Caspase-1 inhibitors ameliorated the severity of展开更多
文摘Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.
文摘目的:炎症反应尤其是炎症小体及炎症细胞因子的过度表达,是影响急性脑梗死发生、发展的重要原因之一,包括脑梗死的起始、梗死后损伤的进展和恢复。本研究主要探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)、白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-18(interleukin-18,IL-18)在急性脑梗死患者血浆中的表达及意义。方法:纳入急性脑梗死患者85例为脑梗死组,根据神经功能缺损严重程度、脑梗死面积及发病后第90天的改良Rankin量表(Modified Rankin Scale,mRS)评分分为轻、中及重度组,小、中及大面积组,预后良好组及预后不良组。纳入同期健康体检者85例为对照组。采用酶联免疫吸附(enzyme-linked immunosorbnent assay,ELISA)法检测AIM2、IL-1β和IL-18在这两组人群血浆中的表达水平。结果:脑梗死组血浆AIM2、IL-1β和IL-18水平均明显高于对照组,差异均具有统计学意义(均P<0.001)。脑梗死组亚组比较示:患者血浆AIM2、IL-1β和IL-18水平在重度神经功能缺损严重程度组>中度组>轻度组,在大面积脑梗死组>中面积组>小面积组,在预后不良组>预后良好组,差异均具有统计学意义(均P<0.05);血浆AIM2水平与美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑梗死面积及mRS评分呈正相关(分别r=0.791、r=0.710、r=0.763,均P<0.001),IL-1β水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.716、r=0.690、r=0.688,均P<0.001),IL-18水平与NIHSS评分、脑梗死面积及mRS评分呈正相关(分别r=0.714、r=0.638、r=0.653,均P<0.001);血浆AIM2与IL-1β、IL-18水平呈正相关(分别r=0.828、r=0.751,均P<0.001)。结论:AIM2、IL-1β和IL-18在急性脑梗死患者血浆中表达上调,而且与急性脑梗死患者的神经功能缺损严重程度、脑梗死面积及预后密切相关,提示AIM2、IL-1β和IL-18可能在急性脑梗死的发生、发展中起重要作用。
文摘Inflammasomes are multiprotein intracellular complexes which are responsible for the activation of inflammatory responses. Among various subtypes of inflammasomes, NLRP3 has been a subject of intensive investigation. NLRP3 is considered to be a sensor of microbial and other danger signals and plays a crucial role in mucosal immune responses, promoting the maturation of proinflammatory cytokines interleukin 1β(IL-1β) and IL-18. NLRP3 inflammasome has been associated with a variety of inflammatory and autoimmune conditions, including inflammatory bowel diseases(IBD). The role of NLRP3 in IBD is not yet fully elucidated as it seems to demonstrate both pathogenic and protective effects. Studies have shown a relationship between genetic variants and mutations in NLRP3 gene with IBD pathogenesis. A complex interaction between the NLRP3 inflammasome and the mucosal immune response has been reported. Activation of the inflammasome is a key function mediated by the innate immune response and in parallel the signaling through IL-1β and IL-18 is implicated in adaptive immunity. Further research is needed to delineate the precise mechanisms of NLRP3 function in regulating immune responses. Targeting NLRP3 inflammasome and its downstream signaling will provide new insights into the development of future therapeutic strategies.
文摘目的检测NLRP3炎性小体及其下游炎性因子IL-1β/IL-18在类风湿性关节炎(rheumatoid arthritis,RA)患者滑膜被覆细胞及滑膜间质中的表达及分布情况,探讨NLRP3炎症复合体在RA免疫调节中的作用机制。方法采用免疫组化EnVision法检测30例RA、10例骨性关节炎(osteoarthritis,OA)患者滑膜被覆细胞及滑膜间质中NLRP3、Caspase-1及其下游炎性因子IL-1β及IL-18的表达。采用Spearman秩相关分析RA患者滑膜组织中NLRP3炎性小体及其下游炎性因子IL-1β/IL-18的表达水平与RA临床和实验室参数的相关性。结果 NLRP3在RA、OA组中的阳性率分别为100.00%和70.00%,Caspase-1在RA、OA组中的阳性率分别为100.00%和50.00%,IL-1β在RA、OA组中的阳性率分别为100.00%和60.00%,IL-18在RA、OA组中的阳性率分别为86.67%和0,NLRP3、Caspase-1、IL-1β及IL-18在RA和OA组间差异均有统计学意义( P <0.05)。IL-1β与RF表达呈显著正相关( P <0.05);NLRP3与CRP、RF、Caspase-1及IL-1β表达均呈显著正相关( P <0.05),而与IL-18表达无相关性( P >0.05)。结论 NLRP3/Caspase-1信号通路因子在RA的发病过程中起重要作用,且与疾病的活动性密切相关。IL-1β的分泌主要是由Caspase-1介导产生,提示抑制NLRP3或Caspase-1可有效下调IL-1β的表达,可能是RA潜在的治疗靶点,具有重要的临床指导意义。
文摘AIM： To assess the therapeutic effect of Caspase-1 inhibitors （ICE-I） on acute lung injury （ALI） in experimental severe acute pancreatitis （SAP）. METHODS： Forty-two SD rats were randomly divided into 3 groups： healthy controls （HC, n = 6）; SAP-S group （n = 18）; SAP-ICE-i group （n = 18）. SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion, in SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum 1L-1β was measured by EUSA. Intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated. RESULTS： Serum IL-1β levels in SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h, which were increased significantly （P 〈 0.01, vs HC）. in SAP- ICE-I group, those values were decreased significantly （P 〈 0.01, vs SAP-S）. intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group （P 〈 0.01, vs HC）. The expression of IL-lβ and IL-18 mRNA were decreased significantly in the SAP- ICE-I group （P 〈 0.01, vs SAP-S）, whereas Caspase-1 mRNA expression had no significant difference （P 〉 0.05）. The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly （P 〈 0.05 at 6 h, P 〈 0.01 at 12 h and 18 h, vs HC） and they were decreased significantly in the SAP-ICE-I group （P 〈 0.05, vs SAP-S）.Caspase-1 inhibitors ameliorated the severity of
