Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18),however,the process of inflammation cascades has not been ...Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18),however,the process of inflammation cascades has not been fully illustrated.The present study aimed to determine the mechanisms of cardiac inflammatory amplification following acute sympathetic activation.With bioinformatics analysis,galectin-3 was identified as a potential key downstream effector of β-AR and IL-18 activation.The serum level of galectin-3 was positively correlated with norepinephrine or IL-18 in patients with chest pain.In the heart of mice treated with β-AR agonist isoproterenol (ISO,5 mg kg^(-1)),galectin-3 expression was upregulated markedly later than IL-18 activation,and Nlrp3^(-/-)and Il18^(-/-)mice did not show ISO-induced galectin-3 upregulation.It was further revealed that cardiomyocyte-derived IL-18 induced galectin-3 expression in macrophages following ISO treatment.Moreover,galectin-3deficiency suppressed ISO-induced cardiac inflammation and fibrosis without blocking ISO-induced IL-18 increase.Treatment with a galectin-3 inhibitor,but not a β-blocker,one day after ISO treatment effectively attenuated cardiac inflammation and injury.In conclusion,galectin-3 is upregulated to exaggerate cardiac inflammation and injury following acute β-AR activation,a galectin-3 inhibitor effectively blocks cardiac injury one day after β-AR insult.展开更多
objective: To investigate whether interleukin-1 receptor-associated kinase-2 (IRAK-2) is involved in interleukin-18 (IL-18)-induced nuclear factor- κ B (NF-κ B) activation. Methods: Phosphorothioate oligodeoxynucleo...objective: To investigate whether interleukin-1 receptor-associated kinase-2 (IRAK-2) is involved in interleukin-18 (IL-18)-induced nuclear factor- κ B (NF-κ B) activation. Methods: Phosphorothioate oligodeoxynucleotide (ODN) was designed antisense to sequences of IRAK-2. Antisense IRAK-2 ODN was delivered by lipofectin encapsulation into cultured HepG2 cells. IRAK-2 mRNA expression was assayed by semiquantitative reverse transcription-PCR. The levels of NF- K B were measured by sandwich ELISA. Results: Antisense IRAK-2 ODN blocked IRAK -2expression. IL-18 activated NT- K B and the A value increased from a basal level of 0.115±0.004 to 2.141 ±0.038. Antisense IRAK-2 ODN inhibited IL-18-induced NT- K B activation in a dose (1-8μg )-dependent fashion. When the cells were treated with 4μg antisense IRAK-2 ODN for 8 h, a maximum inhibition of 45.4% was induced as shown by the reduction of the OD value from a control level of 2.141±0.038 down to 1.168±0.026. Conclusion: IRAK-2 can regulate IL-18-stimulated NF- K B activation.展开更多
旨在探讨雌性山羊腹腔肠系膜前神经节是否存在IL-18受体((Interleukin-18receptor,IL-18R)。取雌性山羊腹腔肠系膜前神经节(Celiac Superior Mesenteric Ganglion,CSMG),通过免疫组化SP法检测IL-18R在CSMG的分布情况。结果显示,雌性山羊...旨在探讨雌性山羊腹腔肠系膜前神经节是否存在IL-18受体((Interleukin-18receptor,IL-18R)。取雌性山羊腹腔肠系膜前神经节(Celiac Superior Mesenteric Ganglion,CSMG),通过免疫组化SP法检测IL-18R在CSMG的分布情况。结果显示,雌性山羊CSMG的神经元、卫星细胞和神经纤维均有IL-18R免疫阳性产物分布,且主要分布于CSMG的神经元胞体,说明雌性山羊CSMG具备对IL-18刺激做出反应的条件。提示:雌性山羊CSMG可能是IL-18对胃肠道免疫内分泌调节与神经调节协调的关键点。展开更多
基金supported by the National Key R&D Program of China (2021YFF0501401)the National Natural Science Foundation of China (82030072)+5 种基金the Michigan Medicine-PKUHSC Joint Institute for Translational and Clinical Research (BMU2019JI007)the Fundamental Research Funds for the Central Universitiesthe National Natural Science Foundation of China (81830009, 81822003)the Beijing Municipal Natural Science Foundation (7191013)the Key Clinical Projects of Peking University Third Hospital (BYSYZD2019022)CAMS Innovation Fund for Medical Sciences to (2021-I2M-5-003)。
文摘Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18),however,the process of inflammation cascades has not been fully illustrated.The present study aimed to determine the mechanisms of cardiac inflammatory amplification following acute sympathetic activation.With bioinformatics analysis,galectin-3 was identified as a potential key downstream effector of β-AR and IL-18 activation.The serum level of galectin-3 was positively correlated with norepinephrine or IL-18 in patients with chest pain.In the heart of mice treated with β-AR agonist isoproterenol (ISO,5 mg kg^(-1)),galectin-3 expression was upregulated markedly later than IL-18 activation,and Nlrp3^(-/-)and Il18^(-/-)mice did not show ISO-induced galectin-3 upregulation.It was further revealed that cardiomyocyte-derived IL-18 induced galectin-3 expression in macrophages following ISO treatment.Moreover,galectin-3deficiency suppressed ISO-induced cardiac inflammation and fibrosis without blocking ISO-induced IL-18 increase.Treatment with a galectin-3 inhibitor,but not a β-blocker,one day after ISO treatment effectively attenuated cardiac inflammation and injury.In conclusion,galectin-3 is upregulated to exaggerate cardiac inflammation and injury following acute β-AR activation,a galectin-3 inhibitor effectively blocks cardiac injury one day after β-AR insult.
文摘objective: To investigate whether interleukin-1 receptor-associated kinase-2 (IRAK-2) is involved in interleukin-18 (IL-18)-induced nuclear factor- κ B (NF-κ B) activation. Methods: Phosphorothioate oligodeoxynucleotide (ODN) was designed antisense to sequences of IRAK-2. Antisense IRAK-2 ODN was delivered by lipofectin encapsulation into cultured HepG2 cells. IRAK-2 mRNA expression was assayed by semiquantitative reverse transcription-PCR. The levels of NF- K B were measured by sandwich ELISA. Results: Antisense IRAK-2 ODN blocked IRAK -2expression. IL-18 activated NT- K B and the A value increased from a basal level of 0.115±0.004 to 2.141 ±0.038. Antisense IRAK-2 ODN inhibited IL-18-induced NT- K B activation in a dose (1-8μg )-dependent fashion. When the cells were treated with 4μg antisense IRAK-2 ODN for 8 h, a maximum inhibition of 45.4% was induced as shown by the reduction of the OD value from a control level of 2.141±0.038 down to 1.168±0.026. Conclusion: IRAK-2 can regulate IL-18-stimulated NF- K B activation.
文摘旨在探讨雌性山羊腹腔肠系膜前神经节是否存在IL-18受体((Interleukin-18receptor,IL-18R)。取雌性山羊腹腔肠系膜前神经节(Celiac Superior Mesenteric Ganglion,CSMG),通过免疫组化SP法检测IL-18R在CSMG的分布情况。结果显示,雌性山羊CSMG的神经元、卫星细胞和神经纤维均有IL-18R免疫阳性产物分布,且主要分布于CSMG的神经元胞体,说明雌性山羊CSMG具备对IL-18刺激做出反应的条件。提示:雌性山羊CSMG可能是IL-18对胃肠道免疫内分泌调节与神经调节协调的关键点。
