期刊文献+
共找到18篇文章
< 1 >
每页显示 20 50 100
Exploring the effect of Bushen Bitong recipe-containing serum on IL-1β-induced chondrocyte apoptosis based on SOX9/NF-κB/MMP-13 signaling pathway
1
作者 YI Lin ZHANG Wen-hao +4 位作者 XIANG Wen-yuan SHI Zheng-yu REMILA Aimai-ti DENG Ying-jie FANG Rui 《Journal of Hainan Medical University》 CAS 2024年第4期1-7,共7页
Objective:To observe the effect and possible mechanism of action of Bushen Bitong recipe(BSBT)containing serum on IL-1β-induced chondrocyte apoptosis.Methods:Generation 3 rat chondrocytes were randomized into Control... Objective:To observe the effect and possible mechanism of action of Bushen Bitong recipe(BSBT)containing serum on IL-1β-induced chondrocyte apoptosis.Methods:Generation 3 rat chondrocytes were randomized into Control,IL-1β,IL-1β+BSBT(L),IL-1β+BSBT(M),and IL-1β+BSBT(H)groups(5%,10%and 15%BSBT-containing serum),and then 24h after intervention respectively,the cell proliferation and Apoptosis rate;Western blot detected the expression levels of Bcl-2,BAX,Caspase-3,SOX9,NF-κB p65,MMP-13 proteins in chondrocytes.ELISA detected the levels of TNF-α,IL-6,and bFGF in the supernatants of chondrocyte culture.Results:Compared with Control group,cell proliferation activity decreased,apoptosis rate increased,NF-κB p65,MMP-13 protein level and TNF-α,IL-6 level increased,and SOX9 protein level and bFGF level decreased in IL-1βgroup;compared with IL-1βgroup,different concentrations of BSBT-containing serum group,cell proliferation activity increased,and apoptosis rate decreased.NF-κB p65,MMP-13 protein level and TNF-α,IL-6 level decreased,SOX9 protein level and bFGF level increased;compared with IL-1β+BSBT(L)group,cell proliferation activity increased,apoptosis rate decreased in IL-1β+BSBT(M)and IL-1β+BSBT(H)groups,and NF-κB p65,MMP-13 protein level and TNF-αlevel decreased.13 protein levels and TNF-αand IL-6 levels decreased,and SOX9 protein levels and bFGF levels increased.Conclusion:BSBT-containing serum may promote IL-1β-induced proliferation of chondrocytes,reduce apoptosis,improve the microenvironment of chondrocytes,and promote cartilage repair through the SOX9/NF-κB/MMP-13 signaling pathway. 展开更多
关键词 Bushen Bitong recipe Osteoarthritis CHONDrOCYTES signaling pathway il-1Β
下载PDF
三七皂苷R1通过miR-181/IL-8/TLR4通路调控糖尿病性视神经病变的机制研究 被引量:2
2
作者 郜会龙 丁来标 +2 位作者 王丽霞 杨洁 宫娇娇 《中国中医眼科杂志》 2023年第11期1014-1020,1034,共8页
目的探究三七皂苷R1(NGR1)通过微小RNA-181/白细胞介素-8/Toll样受体4(miR-181/IL-8/TLR4)通路调控糖尿病性视神经病变(DON)大鼠的作用及抗炎机制。方法尾静脉注射链脲佐菌素建立糖尿病大鼠模型,随机分为模型组(MG)、低剂量NGR1组(LNGR1... 目的探究三七皂苷R1(NGR1)通过微小RNA-181/白细胞介素-8/Toll样受体4(miR-181/IL-8/TLR4)通路调控糖尿病性视神经病变(DON)大鼠的作用及抗炎机制。方法尾静脉注射链脲佐菌素建立糖尿病大鼠模型,随机分为模型组(MG)、低剂量NGR1组(LNGR1)、中剂量NGR1组(MNGR1)、高剂量NGR1组(HNGR1),另设对照组(CG),每组8只,共40只。LNGR1、MNGR1、HNGR1组大鼠每2日灌胃1次,剂量依次为15、30、60 mg/kg的NGR1,CG、MG组大鼠灌胃等体积0.9%氯化钠注射液,连续给药6周,期间监测大鼠血糖及体质量。给药完成后苏木精-伊红(HE)染色观察检测大鼠视神经形态,酶联免疫吸附法(ELISA)检测视神经糖化血红蛋白(HbA1c)、白细胞介素(IL)-1β、IL-6、肿瘤坏死因子α(TNF-α)和基质金属蛋白酶9(MMP-9)水平,实时荧光定量PCR(qRT-PCR)检测视神经miR-181表达,荧光素酶报告试验检测miR-181和IL-8靶向关系,Western Blot法检测视神经IL-8、TLR4的蛋白表达。结果(1)体重、血糖和HbA1c:与CG组比较,MG大鼠体重降低(t=-3.675,P=0.001),血糖、HbA1c较高(t_(血糖)=67.721,t_(HbA1c)=27.213,均P=0.000);与MG组比较,MNGR1、HNGR1组大鼠体重较高(t_(MNGR1)=4.863,t_(HNGR1)=6.018,均P=0.000),血糖较低(t_(MNGR1)=-29.171,t_(HNGR1)=-43.981,均P=0.000),HbA1c较低(t_(MNGR1)=-18.468,t_(HNGR1)=-22.799,均P=0.000),差异均有统计学意义。(2)炎症因子:与CG组比较,MG组大鼠血清IL-1β、IL-6、TNF-α和MMP-9表达较高(t_(IL-1β)=22.949,t_(IL-6)=20.732,t_(TNF-α)=12.785,t_(MMP-9)=12.276,均P=0.000);与MG组比较,LNGR1、MNGR1、HNGR1组大鼠血清IL-1β水平较低(t_(LNGR1)=-6.465,t_(MNGR1)=-18.598,t_(HNGR1)=-21.943,均P=0.000)、IL-6水平较低(t_(LNGR1)=-3.765,P=0.001;t_(MNGR1)=-13.274,t_(HNGR1)=-15.405,均P=0.000)、TNF-α水平较低(t_(MNGR1)=-9.221,t_(HNGR1)=-10.523,均P=0.000)、MMP-9水平较低(t_(LNGR1)=-2.934,P=0.006;t_(MNGR1)=-4.343,t_(HNGR1)=-9.991,均P=0.000),差异均有统计学意义。(3)视神经形态:与CG比较,MG组大鼠视神经出现明显的出血和血管扩张、轴突肿胀以及胶质细胞增生,但LNGR1、MNGR1、HNGR1组以上情况较MG随药物剂量较高改善。与CG组比较,MG组大鼠视神经横截面积较低(t=-27.680,P=0.000),胶质细胞数较高(t=5.501,P=0.000);与MG组比较,LNGR1、MNGR1、HNGR1组大鼠视神经横截面积较大(t_(LNGR1)=6.241,t_(MNGR1)=7.853,t_(HNGR1)=10.248,均P=0.000),HNGR1组胶质细胞数较低(t_(HNGR1)=-3.097,P=0.004),差异均有统计学意义。(5)IL-8与miR-181的靶向关系:miR-181与IL-8存在结合位点。(6)miR-181/IL-8/TLR4通路蛋白:与CG组比较,MG组大鼠视神经miR-181、IL-8、TLR4表达较高(t_(miR-181)=33.870,t_(IL-8)=62.851,t_(TLR4)=20.802,均P=0.000);与MG组比较,LNGR1、MNGR1、HNGR1组大鼠视神经miR-181表达较低(t_(LNGR1)=13.476,t_(MNGR1)=14.420,t_(HNGR1)=11.187,均P=0.000)、IL-8表达较低(t_(LNGR1)=2.460,P=0.019;t_(MNGR1)=19.230,t_(HNGR1)=46.383,均P=0.000)、TLR4表达较低(t_(LNGR1)=8.350,t_(MNGR1)=14.185,t_(HNGR1)=11.502,均P=0.000),差异均有统计学意义。结论NGR1可降低DON大鼠血糖,改善视神经病理状况,其机制可能与调控视神经miR-181/IL-8/TLR4通路及相关炎症有关。 展开更多
关键词 三七皂苷r1 糖尿病性视神经病变 mir-181 tlr4 il-8
下载PDF
IRAK-4在白介素-1受体/Toll样受体(IL-1R/TLRs)介导的炎症信号通路中的关键作用 被引量:7
3
作者 李帆 芮耀诚 《药学实践杂志》 CAS 2011年第1期1-3,14,共4页
白介素-1受体相关激酶4(interleukin-1 receptor-associated kinase 4;IRAK-4)是近年来发现的参与机体先天性免疫反应过程中的关键分子。它与另外3个成员IRAK-1、IRAK-2、IRAK-M同属于IRAK家族,目前经过对IRAK-4分子的激酶活性以及其对... 白介素-1受体相关激酶4(interleukin-1 receptor-associated kinase 4;IRAK-4)是近年来发现的参与机体先天性免疫反应过程中的关键分子。它与另外3个成员IRAK-1、IRAK-2、IRAK-M同属于IRAK家族,目前经过对IRAK-4分子的激酶活性以及其对炎症反应的正向和负向的调控作用的研究表明,IRAK-4分子联系着上下游的信号转导,在TLRs/IL-1R介导的炎症信号通路中的作用更为关键。本文就IRAK-4分子的活性、以及IRAK-4分子在TLRs/IL-1R介导的炎症信号转导通路中的作用作一综述。以期设计出针对IRAK-4特异性的药物,或者通过基因治疗手段干预IRAK-4表达,为感染控制提供新的思路,开发出新的抗炎药物。 展开更多
关键词 白介素-1受体相关激酶4(IrAK-4) tlrs/il-1r信号通路 激酶活性
下载PDF
Ramulus Cinnamomi extract attenuates neuroinflammatory responses via downregulating TLR4/MyD88 signaling pathway in BV2 cells 被引量:5
4
作者 Huan Yang Xiao Cheng +2 位作者 Ying-lin Yang Yue-hua Wang Guan-hua Du 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第11期1860-1864,共5页
Ramulus Cinnamomi (RC), a traditional Chinese herb, has been used to attenuate inflammatory responses. The purpose of this study was to investigate the effect of RC extract on lipopolysaccharide (LPS)-induced neur... Ramulus Cinnamomi (RC), a traditional Chinese herb, has been used to attenuate inflammatory responses. The purpose of this study was to investigate the effect of RC extract on lipopolysaccharide (LPS)-induced neuroinflammation in BV2 microglial cells and the underlying mechanisms involved. BV2 cells were incubated with normal medium (control group), LPS, LPS plus 30 pg/mL RC extract, or LPS plus 100 pg/mL RC extract. The BV2 cell morphology was observed under an optical microscope and cell viability was detected by MTT assay. Nitric oxide level in BV2 cells was detected using Griess regents, and the levels of interleukin-6, interleukin-1 β, and tumor necrosis factor u in BV2 cells were determined by ELISA. The expression levels of cyclooxygenase-2, Toll-like receptor 4 and myeloid differentiation factor 88 proteins were detected by western blot assay. Compared with the LPS group, both 30 and 100 μg/mL RC extract had no significant effect on the viability of BV2 cells. The levels of nitric oxide, interleukin-6, interleukin-1β and tumor necrosis factor ct in BV2 cells were all significantly increased after LPS induction, and the levels were significantly reversed after treatment with 30 and 100 μg/mL RC extract. Furthermore, RC extract significantly inhibited the protein expression levels of cyclooxygenase-2, Toll-like receptor 4 and myeloid differentiation factor 88 in LPS-induced BV2 cells. Our findings suggest that RC extract alleviates neuroinflammation by downregulating the TLR4/MyD88 signaling pathway. 展开更多
关键词 nerve regeneration ramulus Cinnamomi BV2 cells LIPOPOLYSACCHArIDE NEUrOINFLAMMATION pro-inflammatory factors tlr4/ MyD88 signaling pathway nitric oxide INTErLEUKIN-6 INTErLEUKIN-1Β tumor necrosis factor a neuronal regeneration
下载PDF
大黄丹参对急性胰腺炎重症化过程中TLR-IL-1R信号系统影响 被引量:9
5
作者 李钢 赵金锋 +3 位作者 支飞虎 付倩 王凯诚 陈海平 《中国中西医结合外科杂志》 CAS 2013年第3期263-267,共5页
目的:探讨生大黄和丹参治疗重症急性胰腺炎对机体炎症反应和免疫应答关键信号系统TLR-IL-1R信号通路的调控作用。方法:建立SD大鼠实验性重症急性胰腺炎模型,分正常对照组(SO)、实验对照组(SAP)、大黄丹参干预组(DD);检测脾脏组织中β-ar... 目的:探讨生大黄和丹参治疗重症急性胰腺炎对机体炎症反应和免疫应答关键信号系统TLR-IL-1R信号通路的调控作用。方法:建立SD大鼠实验性重症急性胰腺炎模型,分正常对照组(SO)、实验对照组(SAP)、大黄丹参干预组(DD);检测脾脏组织中β-arrestin mRNA的表达、肝脏组织TRAF6蛋白含量水平、胰腺组织中NF-κBp65蛋白表达的水平、血清炎性细胞因子TNF-α、IL-6的活性水平。结果:SAP组β-arrestin mRNA、TRAF6蛋白表达均受到显著抑制,NF-κBp65蛋白、TNF-α、IL-6活性水平表达增强,DD组β-arrestin mRNA下降有抑制,TRAF6蛋白表达进一步下降,NF-κBp65蛋白、TNF-α、IL-6活性水平增强有阻抑。结论:生大黄联合丹参有上调TLR-IL-1R信号系统负调控因子β-arrestin mRNA表达的作用;可以阻止急性胰腺炎重症化进程,其机理与调控制TLR-IL-1R信号系统具有相关性。 展开更多
关键词 急性胰腺炎 tlril-1r Β-ArrESTIN 中药
下载PDF
IRAK-4:TLR/IL-1R家族共同信号转导系统中的关键因子 被引量:8
6
作者 刘作金 刘长安 龚建平 《生理科学进展》 CAS CSCD 北大核心 2005年第3期276-279,共4页
最近发现的一种新的白细胞介素1受体相关激酶4(interleukin1receptorassociatedkinase4,IRAK4)不仅可促使白细胞介素1受体相关激酶1(IRAK1)磷酸化,还是IRAK1募集于TLR/IL1R复合物的必要条件,从而成为调控IRAK1生物活性以及内毒素胞内信... 最近发现的一种新的白细胞介素1受体相关激酶4(interleukin1receptorassociatedkinase4,IRAK4)不仅可促使白细胞介素1受体相关激酶1(IRAK1)磷酸化,还是IRAK1募集于TLR/IL1R复合物的必要条件,从而成为调控IRAK1生物活性以及内毒素胞内信号转导的最关键分子。充分认识IRAK4的作用机制,将有助于设计出新的针对感染性疾病的治疗策略。 展开更多
关键词 tlr/il-1r家族 IrAK-4 天然免疫 信号转导系统
下载PDF
African swine fever virus MGF505-3R inhibits cGAS-STING-mediated IFN-βpathway activation by degrading TBK1 被引量:1
7
作者 Mingyang Cheng Jiawei Luo +14 位作者 Yuetong Duan Yu Yang Chunwei Shi Yu Sun Yiyuan Lu Junhong Wang Xiaoxu Li Jianzhong Wang Nan Wang Wentao Yang Yanlong Jiang Guilian Yang Yan Zeng Chunfeng Wang Xin Cao 《Animal Diseases》 2022年第3期154-164,共11页
African swine fever virus(ASFV)is an important pathogen causing acute infectious disease in domestic pigs and wild boars that seriously endangers the global swine industry.As ASFV is structurally complex and encodes a... African swine fever virus(ASFV)is an important pathogen causing acute infectious disease in domestic pigs and wild boars that seriously endangers the global swine industry.As ASFV is structurally complex and encodes a large number of functional proteins,no effective vaccine has been developed to date.Thus,dissecting the mechanisms of immune escape induced by ASFV proteins is crucial.A previous study showed that the ASFV-encoded protein is an important factor in host immunity.In this study,we identified a negative regulator,MGF505-3R,that significantly downregulated cGAS/STING-and poly(dG:dC)-mediated IFN-βand interferon stimulation response element(ISRE)reporter activity and suppressed IFNB1 and IFIT2 mRNA levels.In addition,TBK1,IRF3 and IκBαphosphorylation levels were also inhibited.Mechanistically,MGF505-3R interacted with cGAS/TBK1/IRF3 and targeted TBK1 for degradation,thereby disrupting the cGAS-STING-mediated IFN-βsignaling pathway,which appears to be highly correlated with autophagy.Knockdown MGF505-3R expression enhanced IFN-βand IL-1βproduction.Taken together,our study revealed a negative regulatory mechanism involving the MGF505-3R-cGAS-STING axis and provided insights into an evasion strategy employed by ASFV that involves autophagy and innate signaling pathways. 展开更多
关键词 African swine fever virus MGF505-3r cGAS/STING signaling pathway TBK1 Innate immunity
下载PDF
The IL-1R/TLR signaling pathway is essential for efficient CD8+ T-cell responses against hepatitis B virus in the hydrodynamic injection mouse model 被引量:7
8
作者 Zhiyong Ma Jia Liu +8 位作者 Weimin Wu Ejuan Zhang Xiaoyong Zhang Qian Li Gennadiy Zelinskyy Jan Buer Ulf Dittmer Carsten J Kirschning Mengji Lu 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2017年第12期997-1008,共12页
The outcome of hepatitis B viral(HBV)infection is determined by the complex interactions between replicating HBV and the immune system.While the role of the adaptive immune system in the resolution of HBV infection ha... The outcome of hepatitis B viral(HBV)infection is determined by the complex interactions between replicating HBV and the immune system.While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively,the contribution of innate immune mechanisms remains to be defined.Here we examined the role of the interleukin-1 receptor/Toll-like receptor(IL-1R/TLR)signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model.Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice(WT)and a panel of mouse strains lacking specific innate immunity component expression.We found higher levels of HBV protein production and replication in Tlr2^(−/−),Tlr23479^(−/−),3d/Tlr24^(−/−),Myd88/Trif^(−/−)and Irak4^(−/−)mice,which was associated with reduced HBV-specific CD8+T-cell responses in these mice.Importantly,HBV clearance was delayed for more than 2 weeks in 3d/Tlr24^(−/−),Myd88/Trif^(−/−)and Irak4^(−/−)mice compared to WT mice.HBV-specific CD8+T-cell responses were functionally impaired for producing the cytokines IFN-γ,TNF-αand IL-2 in TLR signaling-deficient mice compared to WT mice.In conclusion,the IL-1R/TLR signaling pathway might contribute to controlling HBV infection by augmenting HBV-specific CD8+T-cell responses. 展开更多
关键词 CD8^(+)T-cell response Hepatitis B virus il-1r/tlr signaling pathway Toll-like receptor
原文传递
GRK2 overexpression inhibits IGF1-induced proliferation and migration of human hepatocellular carcinoma cells by down-regulating EGR1 被引量:4
9
作者 MA Yang HAN Chen-chen +2 位作者 HUANG Qiong SUN Wu-yi WEI Wei 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1073-1073,共1页
OBJECTIVE To investigate the role and mechanism of G protein-coupled receptor kinase 2(GRK2)involving in hepatocel ular carcinoma(HCC)progression.METHODS Cel Counting Kit 8 and tumor colony formation assay were design... OBJECTIVE To investigate the role and mechanism of G protein-coupled receptor kinase 2(GRK2)involving in hepatocel ular carcinoma(HCC)progression.METHODS Cel Counting Kit 8 and tumor colony formation assay were designed to detect HCC cell proliferation,wound healing assay was to detect HCC migration.The correlation between GRK2 and early growth response-1(EGR1)were detected by RT-PCR and real-time PCR assays.Co-immunoprecipitation and Western blot assay were adopted to detect the relationship between GRK2and insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS In this study we find that GRK2plays an inhibition role in IGF1-induced HCC cell proliferation and migration.Overexpression of GRK2 causes a decrease in EGR1 expression,while knockdown of GRK2 leads to the dramatically increase in EGR1 expression in the treatment of IGF1.Through co-immunoprecipitation and Western blot assay,we confirm that GRK2can interact with IGF-1R and inhibiting IGF1-induced activation of IGF1R signaling pathway.Silencing EGR1attenuates GRK2 overexpression-caused inhibition of cell proliferation,tumor colony number and migrationactivity,while overexpressing of EGR1 restores the antiproliferative and migratory effect by GRK2 overexpression in HCCLM3 cells.CONCLUSION Taken together,these results suggest that GRK2 may inhibit IGF1-induced HCC cell growth and migration through down-regulation of EGR1 and indicate that enforced GRK2 may offer a potential therapeutic approach against HCC. 展开更多
关键词 GrK2 EGr1 IGF1r signaling pathway cell proliferation cell migration
下载PDF
大黄丹参上调β-arrestin基因表达阻止大鼠实验性急性胰腺炎重症化进程 被引量:5
10
作者 李钢 赵金锋 +1 位作者 王凯诚 陈海平 《中华中医药学刊》 CAS 2013年第9期1895-1897,共3页
目的:探讨生大黄和丹参通过上调β-arrestin基因表达,进而影响大鼠实验性急性胰腺炎重症化进程的作用机理。方法:建立SD大鼠实验性重症急性胰腺炎模型,分为正常组(SO)、实验对照组(SAP)、大黄丹参干预组(DD),检测脾脏组织中β-arrestin ... 目的:探讨生大黄和丹参通过上调β-arrestin基因表达,进而影响大鼠实验性急性胰腺炎重症化进程的作用机理。方法:建立SD大鼠实验性重症急性胰腺炎模型,分为正常组(SO)、实验对照组(SAP)、大黄丹参干预组(DD),检测脾脏组织中β-arrestin mRNA的表达、肝脏组织TRAF6蛋白含量水平、胰腺组织中NF-κBp65蛋白表达的水平。结果:SAP组β-arrestin mRNA表达受到显著抑制,DD组出现β-arrestin mRNA表达去阻抑现象;SAP组TRAF6蛋白含量水平呈下降变化,DD组TRAF6蛋白含量水平下降更明显;SAP组NF-κB转录活性增强,DD组NF-κB的活性受到抑制。结论:生大黄和丹参可以阻止急性胰腺炎的重症化进程,其机理与上调β-arrestin基因表达,弱化TLR-IL-1R信号系统的作用相关。 展开更多
关键词 急性胰腺炎 tlril-1r Β-ArrESTIN 生大黄 丹参
下载PDF
β-arrestin基因表达对大鼠实验性急性胰腺炎重症化进程的影响 被引量:1
11
作者 赵金锋 李钢 +1 位作者 王凯诚 陈海平 《浙江医学》 CAS 2013年第7期523-525,528,共4页
目的探讨急性胰腺炎重症化进程与β-arrestin基因抑制Toll样受体-白介素1受体(TLR-IL-1R)系统作用的相关性。方法建立SD大鼠实验性急性胰腺炎模型,分为假手术组(SO)、实验组(SAP);以real-time PCR检测脾脏组织中β-arrestin mRNA的表达,... 目的探讨急性胰腺炎重症化进程与β-arrestin基因抑制Toll样受体-白介素1受体(TLR-IL-1R)系统作用的相关性。方法建立SD大鼠实验性急性胰腺炎模型,分为假手术组(SO)、实验组(SAP);以real-time PCR检测脾脏组织中β-arrestin mRNA的表达,Western blot和免疫组化检测肝脏组织TRAF6蛋白和胰腺组织中NF-κBp65蛋白表达。结果与SO组比较,SAP组β-arrestin mRNA表达受到显著抑制TRAF6蛋白表达下降;NF-κBp65转录活性增强(P<0.05或0.01)。结论TLR-IL-1R系统可能参与急性胰腺炎重症化的病理过程。 展开更多
关键词 急性胰腺炎 tlril-1r Β-ArrESTIN
下载PDF
小分子IRAK-4抑制剂的研究进展 被引量:1
12
作者 陈钊 张亚鲁 +1 位作者 马阳 孙铁民 《中南药学》 CAS 2015年第10期1017-1024,共8页
白细胞介素-1受体相关激酶4(interleukin-1 receptor-associated kinase 4,IRAK-4)是细胞内丝氨酸-苏氨酸激酶IRAK家族的成员之一。IRAK-4作为Toll样受体与白介素-1受体信号传导通路下游的关键因子,在全身炎症反应中起非常重要的作用。... 白细胞介素-1受体相关激酶4(interleukin-1 receptor-associated kinase 4,IRAK-4)是细胞内丝氨酸-苏氨酸激酶IRAK家族的成员之一。IRAK-4作为Toll样受体与白介素-1受体信号传导通路下游的关键因子,在全身炎症反应中起非常重要的作用。现已发现,许多慢性疾病也与介导炎症的信号异常有关,对于各种炎症相关性疾病,IRAK-4可以作为一个有效的潜在治疗靶点。因此,研究和开发结构新颖的IRAK-4抑制剂,对于炎症相关性疾病的靶向治疗,具有重要意义。本文就不同类型的小分子IRAK-4抑制剂的研究进展作一综述。 展开更多
关键词 白细胞介素-1受体相关激酶4 tlrs/il-1r信号通路 IrAK-4抑制剂
下载PDF
Sphingosine kinase 1 promotes growth of glioblastoma by increasing inflammation mediated by the NF-κB/IL-6/STAT3 and JNK/PTX3 pathways 被引量:3
13
作者 Wan Li Hongqing Cai +9 位作者 Liwen Ren Yihui Yang Hong Yang Jinyi Liu Sha Li Yizhi Zhang Xiangjin Zheng Wei Tan Guanhua Du Jinhua Wang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2022年第12期4390-4406,共17页
Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence rate.Currently,mechanisms of GBM are still unclear and there is no effectiv... Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence rate.Currently,mechanisms of GBM are still unclear and there is no effective drug for GBM in the clinic.Therefore,it is urgent to identify new drug targets and corresponding drugs for GBM.In this study,in silico analyses and experimental data show that sphingosine kinase 1(SPHK1)is up-regulated in GBM patients,and is strongly correlated with poor prognosis and reduced overall survival.Overexpression of SPHK1 promoted the proliferation,invasion,metastasis,and clonogenicity of GBM cells,while silencing SPHK1 had the opposite effect.SPHK1 promoted inflammation through the NF-κB/IL-6/STAT3 signaling pathway and led to the phosphorylation of JNK,activating the JNK-JUN and JNK-ATF3 pathways and promoting inflammation and proliferation of GBM cells by transcriptional activation of PTX3.SPHK1 interacted with PTX3 and formed a positive feedback loop to reciprocally increase expression,promote inflammation and GBM growth.Inhibition of SPHK1 by the inhibitor,PF543,also decreased tumorigenesis in the U87-MG and U251-MG SPHK1 orthotopic mouse models.In summary,we have characterized the role and molecular mechanisms by which SPHK1 promotes GBM,which may provide opportunities for SPHK1-targeted therapy. 展开更多
关键词 GLIOBLASTOMA Drug target SPHK1 INFLAMMATION NF-κB/il-6/STAT3 signal pathway ATF3 PXT3
原文传递
白细胞介素-1受体相关激酶与消化系统疾病相关性的研究进展
14
作者 邓晓 王朝霞(指导) 《中国免疫学杂志》 CAS CSCD 北大核心 2021年第3期376-381,F0004,共7页
白细胞介素-1受体相关激酶(IRAK)作为在Toll样受体(TLR)及白介素-1受体(IL-1R)介导的信号通路的重要连接体,在信号通路中发挥重要作用,对炎症反应起正向或负向调节作用。近年来的研究表明IRAKs参与了炎症性肠病、酒精性肝病、炎症相关... 白细胞介素-1受体相关激酶(IRAK)作为在Toll样受体(TLR)及白介素-1受体(IL-1R)介导的信号通路的重要连接体,在信号通路中发挥重要作用,对炎症反应起正向或负向调节作用。近年来的研究表明IRAKs参与了炎症性肠病、酒精性肝病、炎症相关性结直肠肿瘤等消化系统疾病的发生发展。本文就IRAKs家族的分子特点、作用机制及其与消化系统疾病的关系研究进展加以综述,有助于揭示疾病的发生机制,为疾病的治疗提供理论依据。 展开更多
关键词 白细胞介素-1受体相关激酶 tlr il-1r 消化系统疾病
下载PDF
Intervention effect and mechanism of Jisheng Shenqi Decoction plus Panax notoginseng and Bionjia on CCl4-induced hepatic fibrosis rat model
15
作者 Zhen-Kang Zhong Xiao-Ling Zhou +3 位作者 Yue-Ming Wang Teng Wu Shi-Yin Lu Xin-Hui Shen 《Journal of Hainan Medical University》 2022年第10期20-26,共7页
Objective:To investigate the intervention effect and specific mechanism of Jisheng Shenqi Decoction plus Panax notoginseng and Turmeric on carbon tetrachloride(CCl4)-induced liver fibrosis in rats.Methods:SPF SD rats ... Objective:To investigate the intervention effect and specific mechanism of Jisheng Shenqi Decoction plus Panax notoginseng and Turmeric on carbon tetrachloride(CCl4)-induced liver fibrosis in rats.Methods:SPF SD rats were randomly divided into control group,model group,and Chinese medicine treatment(low,medium and high dose)groups.The model group and Chinese medicine treatment group were given intraperitoneal injection of 40%CCl4 olive oil solution twice a week.A rat model of liver fibrosis was replicated by the method for 8 weeks.After successful modeling,each drug-administered group was gavaged with corresponding drugs,and the control group and model group were gavaged with equal volume of distilled water,once a day,for 4 weeks.After the last intragastric administration,HE staining and Masson staining were used to observe the pathological morphology of liver tissue,and liver function(ALT,AST)was detected;ELISA method was used to determine transforming growth factorβ(TGF-β),angiotensin II(Ang-Ⅱ),chitinase 3-like protein 1(CHI3L1),interleukin-1(IL-1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)content;The expression levels of type I,type III collagen(Col-Ⅰ,Col-Ⅲ)and TGF-βmRNA were determined by RT-PCR.Results:①HE and Masson staining showed that a large number of liver cells in the model group were inflamed and necrotic,the collagen fibers in the liver tissue were extensively proliferated,the fibrous septa were interconnected,and the pseudolobules were formed.Compared with the model group,the levels of ALT,AST,TGF-β,Ang-Ⅱ,CHI3L1,IL-1,IL-6 and TNF-αin the traditional Chinese medicine treatment group were decreased,while the levels of Col-Ⅰ,Col-ⅢThe expressions ofⅢand TGF-βmRNA were decreased,and the effect was most obvious in the middle and high dose groups of traditional Chinese medicine(P<0.01).Conclusion:Jisheng Shenqi Decoction combined with Panax notoginseng and Biejia can significantly improve liver fibrosis induced by CCl4 in rats,and its mechanism may be related to the down-regulation of angiotensin-converting enzyme(ACE)-angiotensin II(Ang-II)-angiotensin II receptor 1(AT1R)signaling pathway related gene expression,reducing the level of related cytokines,promoting the degradation of extracellular matrix and so on. 展开更多
关键词 Jisheng Shenqi decoction with Panax notoginseng and Turtle shell Liver fibrosis rats ACE-AngⅡ-AT1r signaling pathway
下载PDF
白细胞介素-1受体相关激酶4小分子抑制剂的研究进展 被引量:2
16
作者 余竞成 董正川 +3 位作者 穆瑞旭 陈乐园 李祎亮 侯文彬 《药学学报》 CAS CSCD 北大核心 2023年第1期27-38,共12页
白细胞介素-1受体相关激酶4 (interleukin-1 receptor associated kinase 4, IRAK-4)作为一种丝氨酸-苏氨酸激酶,是转导IL-1R家族和TLRs信号通路的关键信号节点。研究发现IRAK-4介导的炎症通路可以引起人体的关节、肠道、肝脏和神经系... 白细胞介素-1受体相关激酶4 (interleukin-1 receptor associated kinase 4, IRAK-4)作为一种丝氨酸-苏氨酸激酶,是转导IL-1R家族和TLRs信号通路的关键信号节点。研究发现IRAK-4介导的炎症通路可以引起人体的关节、肠道、肝脏和神经系统的炎症反应及其他自身免疫疾病,也是一些癌症细胞的耐药性原因。因此, IRAK-4可以作为炎症疾病和癌症的有效治疗靶点。研发结构新颖的IRAK-4小分子抑制剂,考察其安全性和有效性,丰富对炎症和癌症疾病的临床治疗用药,是该通路药物发展的方向。本文按不同结构分类概述了关于IRAK-4信号通路小分子抑制剂的最新研究进展,旨在为相关药物的研发工作提供参考。 展开更多
关键词 白细胞介素-1受体相关激酶4 tlrs/il-1r信号通路 炎症性疾病 抗肿瘤 小分子抑制剂
原文传递
Complex interaction of adiponectin-mediated pathways on cancer treatment: a novel therapeutic target 被引量:1
17
作者 Massimo Monks Foivos Irakleidis Peng H.Tan 《Journal of Cancer Metastasis and Treatment》 2019年第3期108-130,共23页
Obesity has the far reaching consequence on cancer pathogenesis and immune reactions.In particular,adiponectin(APN)produced by adipocytes played an important role in modulating obesity related malignancies.Via its int... Obesity has the far reaching consequence on cancer pathogenesis and immune reactions.In particular,adiponectin(APN)produced by adipocytes played an important role in modulating obesity related malignancies.Via its interaction with corresponding receptors and their downstream signalling pathways,it regulates cells survival,apoptosis and cancer metastasis.Our review dissects the clinical evidence on how hypoadiponectinaemia associated with the increased risks of several cancers and the long-term prognosis and also addresses the controversies.APN also has its indirect effect on anti-cancer immune response which may influence the disease process.We also analyse the impact of APN on the immune system,the anti-tumour responses and the controversies surrounding this area.Targeting therapeutics on APN and its receptor axis represents a promising and novel anti-cancer treatment.Biological understanding of how APN and its interaction with its receptors may affect the immune reactivity.Careful strategizing the use of APN therapeutics in cancer treatment is important,as the APN receptor signalling on the immune cells can blunt anti-tumour response.Targeting APN or its receptors has an enormous implication for the treatment of cancers. 展开更多
关键词 ADIPONECTIN Adipor1/r2 CANCEr signaling pathway anti-tumor immunity therapeutic targets
原文传递
TLR2刺激对新生儿免疫反应的影响
18
作者 刘建华 《国际免疫学杂志》 CAS 2006年第4期268-268,共1页
关键词 免疫反应 tlr2 新生儿 病原体相关分子模式 molecular 慢性呼吸道疾病 pattern 支气管哮喘 机体免疫应答 il-1r
原文传递
上一页 1 下一页 到第
使用帮助 返回顶部