To explore the expression and clinical significance of molecular chaperone heat shock protein 90 （HSP90） in peripheral blood mononuclear cells （PBMC） and plasma level of interleukin-6 （IL-6） in patients with sys...To explore the expression and clinical significance of molecular chaperone heat shock protein 90 （HSP90） in peripheral blood mononuclear cells （PBMC） and plasma level of interleukin-6 （IL-6） in patients with systemic lupus erythematosus （SLE）, HSP90 was detected in PBMC by Western blot assay and the plasma level of IL-6 was measured by ELISA in 38 SLE patients and 20 normal controls. The correlation analysis was performed between the SLE disease activity index （SLEDAI） and the expression of HSP90 and IL-6. The results show.ed that there was increased expression of HSP90 in the SLE patients. The active SLE group exhibited higher HSP90 levels （0.82±0.10） than the inactive SLE group （0.54±0.09） （P〈0.01）. The expression of HSP90 in normal control group （0.37±0.11） showed significant statistical difference as compared to both the inactive and active SLE groups （P〈0.01, P〈0.01, respectively）. The plasma level of IL-6 exhibited a significant increase in both the inactive and active SLE groups （28.99±1.74 pg/mL, 44.58±9.15 pg/mL, respectively） compared with normal control group （P〈0.01, P〈0.01, respectively）. The expression of HSP90 and IL-6 in SLE patients showed significant positive correlation with SLEDAI scoring （r=0.80, P〈0.01： r= 0.74, P〈0.01, respectively）. In addition, there was a positive correlation between the level of IL-6 and HSP90 in SLE patients （r= 0.86, P〈0.01）. The increased expression of molecular chaperone HSP90 and IL-6 may play an important role in the pathogenesis of SLE by regulating autoimmunity.展开更多
目的探讨特异性组蛋白去乙酰化酶6(HDAC6)抑制剂Tubastatin A Hcl对支气管哮喘(哮喘)小鼠气道炎症的作用及Tubastatin A Hcl调控HDAC6/热休克蛋白90(HSP90)/κB抑制因子激酶(IKK)/核因子κB(NF-κB)信号通路治疗哮喘小鼠气道炎症的分子...目的探讨特异性组蛋白去乙酰化酶6(HDAC6)抑制剂Tubastatin A Hcl对支气管哮喘(哮喘)小鼠气道炎症的作用及Tubastatin A Hcl调控HDAC6/热休克蛋白90(HSP90)/κB抑制因子激酶(IKK)/核因子κB(NF-κB)信号通路治疗哮喘小鼠气道炎症的分子机制。方法本研究为实验性研究。6~8周SPF级雌性BALB/C小鼠随机分为4组:正常组、哮喘组、地塞米松组、Tubastatin A Hcl组,每组6只。哮喘小鼠模型的构建使用卵清蛋白致敏和卵清蛋白激发的方式。测定各组小鼠气道阻力以评估气道反应性。采用HE、AB-PAS和Masson染色观察各组小鼠气道炎症细胞浸润、黏液分泌、气道上皮杯状细胞增生以及气道周围胶原沉积情况。免疫组织化学染色检测各组小鼠肺组织中磷酸化IKK和磷酸化NF-κB的表达分布。蛋白质印迹法检测各组小鼠肺组织中HDAC6、磷酸化IKK、磷酸化NF-κB、IKK和NF-κB的表达水平。免疫沉淀技术检测各组小鼠肺组织中HSP90乙酰化水平变化情况。结果(1)哮喘小鼠模型构建及气道炎症水平检测:与正常组相比,哮喘组小鼠气道高反应性增高;与哮喘组相比,地塞米松组和Tubastatin A Hcl组小鼠气道高反应性降低;HE、AB-PAS和Masson染色结果显示,与正常组相比,哮喘组小鼠气道周围出现大量炎性细胞浸润,气道内可见黏液分泌,气道上皮杯状细胞增生明显,上皮下胶原纤维沉积增加。与哮喘组相比,地塞米松组和Tubastatin A Hcl组小鼠气道炎症、气道上皮杯状细胞增生以及气道周围胶原沉积水平降低。(2)小鼠肺组织中HDAC6表达水平及HSP90乙酰化水平:与正常组相比,哮喘组小鼠肺组织中HDAC6表达水平升高;Tubastatin A Hcl干预后小鼠肺组织中HDAC6表达水平降低。与正常组相比,哮喘组小鼠肺组织中HSP90乙酰化水平降低;Tubastatin A Hcl干预后小鼠肺组织中HSP90乙酰化水平升高。(3)小鼠肺组织中IKK和NF-κB磷酸化水平:与正常组相比,哮喘组小鼠肺组织中IKK和NF-κB磷酸化水平升高;Tubastatin A Hcl干预后小鼠肺组织中IKK和NF-κB磷酸化水平均降低。结论特异性HDAC6抑制剂Tubastatin A Hcl能够有效缓解哮喘小鼠的气道炎症,其机制可能与Tubastatin A Hcl上调HSP90乙酰化水平,进而抑制IKK/NF-κB信号通路有关。展开更多
Background Nicotine,a major component of tobacco,is the main cause of smoking addiction.It was found that asthmatic patients who smoke were insensitive to glucocorticoid treatment.In this paper,we investigated whether...Background Nicotine,a major component of tobacco,is the main cause of smoking addiction.It was found that asthmatic patients who smoke were insensitive to glucocorticoid treatment.In this paper,we investigated whether nicotine could inhibit histone deacetylase 6 activity （HDAC6） and chaperone-dependent activation of the glucocorticoid receptor （GR） in A549 cells.Furthermore,the expression level of heat shock protein 90 （HSP90） was determined.Methods Quantitative real-time polymerase chain reaction was used to detect the levels of RNA transcription,and Western blotting was applied to analyze the levels of protein expression of HDAC6,GR,and HSP90 in A549 cells.Moreover,the effects of dexamethasone and trichostatin A were observed in A549 cells.Results A549 cell proliferation was inhibited in the presence of nicotine,and the level of RNA and protein expression of HDAC6 and GR were down-regulated.Conclusions Nicotine could inhibit HDAC6 activity and chaperone-dependent activation of GR.This might be the main reason why asthmatic patients who smoke show insensitivity to the glucocorticoid treatment.展开更多
文摘To explore the expression and clinical significance of molecular chaperone heat shock protein 90 （HSP90） in peripheral blood mononuclear cells （PBMC） and plasma level of interleukin-6 （IL-6） in patients with systemic lupus erythematosus （SLE）, HSP90 was detected in PBMC by Western blot assay and the plasma level of IL-6 was measured by ELISA in 38 SLE patients and 20 normal controls. The correlation analysis was performed between the SLE disease activity index （SLEDAI） and the expression of HSP90 and IL-6. The results show.ed that there was increased expression of HSP90 in the SLE patients. The active SLE group exhibited higher HSP90 levels （0.82±0.10） than the inactive SLE group （0.54±0.09） （P〈0.01）. The expression of HSP90 in normal control group （0.37±0.11） showed significant statistical difference as compared to both the inactive and active SLE groups （P〈0.01, P〈0.01, respectively）. The plasma level of IL-6 exhibited a significant increase in both the inactive and active SLE groups （28.99±1.74 pg/mL, 44.58±9.15 pg/mL, respectively） compared with normal control group （P〈0.01, P〈0.01, respectively）. The expression of HSP90 and IL-6 in SLE patients showed significant positive correlation with SLEDAI scoring （r=0.80, P〈0.01： r= 0.74, P〈0.01, respectively）. In addition, there was a positive correlation between the level of IL-6 and HSP90 in SLE patients （r= 0.86, P〈0.01）. The increased expression of molecular chaperone HSP90 and IL-6 may play an important role in the pathogenesis of SLE by regulating autoimmunity.
文摘目的探讨特异性组蛋白去乙酰化酶6(HDAC6)抑制剂Tubastatin A Hcl对支气管哮喘(哮喘)小鼠气道炎症的作用及Tubastatin A Hcl调控HDAC6/热休克蛋白90(HSP90)/κB抑制因子激酶(IKK)/核因子κB(NF-κB)信号通路治疗哮喘小鼠气道炎症的分子机制。方法本研究为实验性研究。6~8周SPF级雌性BALB/C小鼠随机分为4组:正常组、哮喘组、地塞米松组、Tubastatin A Hcl组,每组6只。哮喘小鼠模型的构建使用卵清蛋白致敏和卵清蛋白激发的方式。测定各组小鼠气道阻力以评估气道反应性。采用HE、AB-PAS和Masson染色观察各组小鼠气道炎症细胞浸润、黏液分泌、气道上皮杯状细胞增生以及气道周围胶原沉积情况。免疫组织化学染色检测各组小鼠肺组织中磷酸化IKK和磷酸化NF-κB的表达分布。蛋白质印迹法检测各组小鼠肺组织中HDAC6、磷酸化IKK、磷酸化NF-κB、IKK和NF-κB的表达水平。免疫沉淀技术检测各组小鼠肺组织中HSP90乙酰化水平变化情况。结果(1)哮喘小鼠模型构建及气道炎症水平检测:与正常组相比,哮喘组小鼠气道高反应性增高;与哮喘组相比,地塞米松组和Tubastatin A Hcl组小鼠气道高反应性降低;HE、AB-PAS和Masson染色结果显示,与正常组相比,哮喘组小鼠气道周围出现大量炎性细胞浸润,气道内可见黏液分泌,气道上皮杯状细胞增生明显,上皮下胶原纤维沉积增加。与哮喘组相比,地塞米松组和Tubastatin A Hcl组小鼠气道炎症、气道上皮杯状细胞增生以及气道周围胶原沉积水平降低。(2)小鼠肺组织中HDAC6表达水平及HSP90乙酰化水平:与正常组相比,哮喘组小鼠肺组织中HDAC6表达水平升高;Tubastatin A Hcl干预后小鼠肺组织中HDAC6表达水平降低。与正常组相比,哮喘组小鼠肺组织中HSP90乙酰化水平降低;Tubastatin A Hcl干预后小鼠肺组织中HSP90乙酰化水平升高。(3)小鼠肺组织中IKK和NF-κB磷酸化水平:与正常组相比,哮喘组小鼠肺组织中IKK和NF-κB磷酸化水平升高;Tubastatin A Hcl干预后小鼠肺组织中IKK和NF-κB磷酸化水平均降低。结论特异性HDAC6抑制剂Tubastatin A Hcl能够有效缓解哮喘小鼠的气道炎症,其机制可能与Tubastatin A Hcl上调HSP90乙酰化水平,进而抑制IKK/NF-κB信号通路有关。
文摘Background Nicotine,a major component of tobacco,is the main cause of smoking addiction.It was found that asthmatic patients who smoke were insensitive to glucocorticoid treatment.In this paper,we investigated whether nicotine could inhibit histone deacetylase 6 activity （HDAC6） and chaperone-dependent activation of the glucocorticoid receptor （GR） in A549 cells.Furthermore,the expression level of heat shock protein 90 （HSP90） was determined.Methods Quantitative real-time polymerase chain reaction was used to detect the levels of RNA transcription,and Western blotting was applied to analyze the levels of protein expression of HDAC6,GR,and HSP90 in A549 cells.Moreover,the effects of dexamethasone and trichostatin A were observed in A549 cells.Results A549 cell proliferation was inhibited in the presence of nicotine,and the level of RNA and protein expression of HDAC6 and GR were down-regulated.Conclusions Nicotine could inhibit HDAC6 activity and chaperone-dependent activation of GR.This might be the main reason why asthmatic patients who smoke show insensitivity to the glucocorticoid treatment.
