The expression of molecular chaperone HSP90 and IL-6 in patients with systemic lupus erythematosus

Abstract

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 (SLE-DAI) and the expression of HSP90 and IL-6. The results showed 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.

Keywords

systemic lupus erythematosus / heat shock protein 90 / interleukin-6

References

[1] ZhangJ., TianB.. HSPs and their biological function. Overseas Medicine (Surgery) (Chinese), 2003, 30(5): 265-268

[2] StephanouA., AminV., IsenbergD. A., et al.. Interleukin 6 activates heat-shock protein 90 beta gene expression. Biochem J, 1997, 321(Pt1): 103-106

[3] ShenG. X.. Separation and purification of peripheral blood mononuclear cells. Modern experimental technology of immunology, 19982th ed.Wuhan, Hubei Science and Technology Publishing Company: 377-390

[4] FauldsG., ConroyS., MadaioM., et al.. Increased levels of antibodies to heat shock proteins with increasing age in Mrl/Mp-lpr/lpr mice. Br J Rheumatol, 1995, 34(7): 610-615

[5] LiJ. H., HanS. X., GaoK. B., et al.. Study of HSP90 and its subgroup mRNA in lupus nephritis patient. Chin J Kassa Dermatol (Chinese), 2005, 21(1): 1-3

[6] KenderovA., MinkovaV., MihailovaD., et al.. Lupus-specific kidney deposits of HSP90 are associated with altered IgG idiotypic interactions of anti-HSP90 autoantibodies. Clin Exp Immunol, 2002, 129(1): 169-176

[7] ZengL. X., YeR. G., SunL., et al.. The observation of over expression of IL-6 in PBMC in vivo of the lupus nephritis patients. Chin J Microbiol Immunol (Chinese), 1997, 17(6): 442-445

[8] YangG. Y., LiuH. T., LiS. M., et al.. The impact of IL-6 gene dosaging on pathogenesis of BXSB lupus mice. Chin J Dermatol (Chinese), 1999, 32(1): 22-24

[9] StephanouA., ConroyS., IsenbergD. A., et al.. Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDa heat shock protein (HSP90) and the production of anti-HSP90 antibodies. J Autoimmun, 1998, 11(3): 249-253

[10] PramanikR., JorgensenT. N., XinH., et al.. Interleukin-6 induces expression of Ifi202, an interferon-inducible candidate gene for lupus susceptibility. J Biol Chem, 2004, 279(16): 16121-16127

[11] StephanouA., IsenbergD. A., AkiraS., et al.. The NF-IL6 and STAT-3 signalling pathways co-operate to mediate the activation of the HSP90βgene by IL-6 but have opposite effects on its inducibility by heat shock. Biochem J, 1998, 330(Pt1): 189-195