NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with n...NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.展开更多
肉桂Cinnamomum cassia为樟科樟属植物,其干燥树皮、干燥嫩枝为中医临床常用药材,具有补火助阳、温里散寒的功效。近年来研究发现肉桂及其活性成分肉桂醛、反式肉桂醛、2′-羟基肉桂醛、2′-苯甲酰氧肉桂醛等具有良好的抗炎、解热镇痛...肉桂Cinnamomum cassia为樟科樟属植物,其干燥树皮、干燥嫩枝为中医临床常用药材,具有补火助阳、温里散寒的功效。近年来研究发现肉桂及其活性成分肉桂醛、反式肉桂醛、2′-羟基肉桂醛、2′-苯甲酰氧肉桂醛等具有良好的抗炎、解热镇痛、抗肿瘤、降糖等多种药理活性。基于中医药传统理论及现代医学研究,从调控细胞炎症分子、核因子-κB(nuclear factor-κB,NF-κB)、丝裂原激活的蛋白激酶(mitogenactivated protein kinase,MAPK)、酪氨酸激酶(Janus kinase,JAK)/信号传导与转录活化因子(signal transducer and activator of transcription,STAT)信号通路等方面,对肉桂及其活性成分治疗神经炎、关节炎、动脉粥样硬化等炎症性疾病作用机制的研究进展进行综述,为肉桂的深入研究及其在医药和保健品的应用开发提供参考。展开更多
The immunocytes microglia in the central nervous system （CNS） were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. P...The immunocytes microglia in the central nervous system （CNS） were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. Previous studies showed that purinoceptor P2Y6 mainly contributed to microglia activation and their later phagocytosis in CNS, while in immune system, it participated in the secretion of interleukin （IL）-8 from monocytes and macrocytes. So there raises a question： whether purinoceptor P2Y6 also takes part in neuroinflammation？ Thus, this review mainly concerns about the properties and roles of purinoceptor P2Y6, including （1） structure of purinoceptor P2Y6; （2） distribution and properties of purinoceptor P2Y6; （3） relationships between purinoceptor P2Y6 and microglia; （4） relationships between purinoceptor P2Y6 and immunoinflammation. It＇s proposed that purinoceptor P2Y6 may play a role in neuroinflammation in CNS, although further research is still required.展开更多
基金Supported by National Natural Science Foundation of China, No.81025015,30921006,91129301
文摘NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.
文摘肉桂Cinnamomum cassia为樟科樟属植物,其干燥树皮、干燥嫩枝为中医临床常用药材,具有补火助阳、温里散寒的功效。近年来研究发现肉桂及其活性成分肉桂醛、反式肉桂醛、2′-羟基肉桂醛、2′-苯甲酰氧肉桂醛等具有良好的抗炎、解热镇痛、抗肿瘤、降糖等多种药理活性。基于中医药传统理论及现代医学研究,从调控细胞炎症分子、核因子-κB(nuclear factor-κB,NF-κB)、丝裂原激活的蛋白激酶(mitogenactivated protein kinase,MAPK)、酪氨酸激酶(Janus kinase,JAK)/信号传导与转录活化因子(signal transducer and activator of transcription,STAT)信号通路等方面,对肉桂及其活性成分治疗神经炎、关节炎、动脉粥样硬化等炎症性疾病作用机制的研究进展进行综述,为肉桂的深入研究及其在医药和保健品的应用开发提供参考。
基金supported by the Key Scientific Research Innovation Program of Shanghai Municipal Education Commission,China (No.082260)
文摘The immunocytes microglia in the central nervous system （CNS） were reported to play a crucial role in neurodegeneration. As a member of P2 receptors family, purinoceptor P2Y6 has attracted much attention recently. Previous studies showed that purinoceptor P2Y6 mainly contributed to microglia activation and their later phagocytosis in CNS, while in immune system, it participated in the secretion of interleukin （IL）-8 from monocytes and macrocytes. So there raises a question： whether purinoceptor P2Y6 also takes part in neuroinflammation？ Thus, this review mainly concerns about the properties and roles of purinoceptor P2Y6, including （1） structure of purinoceptor P2Y6; （2） distribution and properties of purinoceptor P2Y6; （3） relationships between purinoceptor P2Y6 and microglia; （4） relationships between purinoceptor P2Y6 and immunoinflammation. It＇s proposed that purinoceptor P2Y6 may play a role in neuroinflammation in CNS, although further research is still required.
