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
Elevated expression of heat shock protein 90 （HSP90） has been found in kidneys and serum of systemic lupus erythematosus （SLE） patients and MRLIMp-FasIprIFasJpr（MRLIIpr） autoimmune mice. We investigated if inhib...Elevated expression of heat shock protein 90 （HSP90） has been found in kidneys and serum of systemic lupus erythematosus （SLE） patients and MRLIMp-FasIprIFasJpr（MRLIIpr） autoimmune mice. We investigated if inhibition of HSP90 would reduce disease in MRL/ Ipr mice. In vitro, pretreatment of mesangial cells with HSP90 inhibitor Geldanamycin prior to immune-stimulation showed reduced expression of IL-6, IL-12 and NO. In vivo, we found HSP90 expression was elevated in MRL/Ipr kidneys when compared to C57BL/6 mice and MRIJIpr mice treated with HSP90 inhibitor 17-DMAG. MRIJIpr mice treated with 17-DMAG showed decreased proteinuria and reduced serum anti-dsDNA antibody production. Glomerulonephritis and glomerular IgG and C3 were not significantly affected by administration of 17-DMAG in MRIJIpr. 17-DMAG increased CD8＋ T cells, reduced double-negative T cells, decreased the CD4/CD8 ratio and reduced follicular B cells. These studies suggest that HSP90 may play a role in regulating T-cell differentiation and activation and that HSP90 inhibition may reduce inflammation in lupus.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Elevated expression of heat shock protein 90 （HSP90） has been found in kidneys and serum of systemic lupus erythematosus （SLE） patients and MRLIMp-FasIprIFasJpr（MRLIIpr） autoimmune mice. We investigated if inhibition of HSP90 would reduce disease in MRL/ Ipr mice. In vitro, pretreatment of mesangial cells with HSP90 inhibitor Geldanamycin prior to immune-stimulation showed reduced expression of IL-6, IL-12 and NO. In vivo, we found HSP90 expression was elevated in MRL/Ipr kidneys when compared to C57BL/6 mice and MRIJIpr mice treated with HSP90 inhibitor 17-DMAG. MRIJIpr mice treated with 17-DMAG showed decreased proteinuria and reduced serum anti-dsDNA antibody production. Glomerulonephritis and glomerular IgG and C3 were not significantly affected by administration of 17-DMAG in MRIJIpr. 17-DMAG increased CD8＋ T cells, reduced double-negative T cells, decreased the CD4/CD8 ratio and reduced follicular B cells. These studies suggest that HSP90 may play a role in regulating T-cell differentiation and activation and that HSP90 inhibition may reduce inflammation in lupus.
