Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis.
Bottom Line: Cathepsins are involved in a variety of physiological processes including antigen processing and presentation and extracellular matrix degradation.In the present study, we evaluated whether expression levels of cathepsins S and B and their inhibitors cystatins B and C are affected by multiple sclerosis (MS) disease state (relapse and remission) and therapies (interferon-β [IFN-β] and the glucocorticoid [GC] methylprednisolone), and whether they are associated with the IFN-β response phenotype.Interestingly, pre-treatment serum cathepsin S/cystatin C ratio was higher in 'good responders' to IFN-β therapy compared to patients without a good response (by 94%, P = 0.003).
Affiliation: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.Show MeSH
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Mentions: IFN-β therapy led to a significant but mild increase in the RNA levels of CTSB (16% increase, P= 0.03), and a much more prominent and significant increase in the cystatin genes CSTC (48% increase, P= 0.011) and CSTB (44% increase, P= 0.004) in PBLs (n= 16) (Fig. 3A). CTSS RNA levels did not change significantly following IFN-β treatment; however, paired analysis revealed a decrease in serum cathepsin S protein levels following IFN-β treatment in the majority of patients (19/25 patients displayed decreased levels, overall 16% decrease of median, P= 0.006) (Fig. 3B). Notably, IFN-β treatment did not affect significantly either pro-cathepsin B or cystatin C serum protein levels. Thus, the overall effect of IFN-β therapy was a small but significant decrease of the cathepsin S to cystatin C ratio in the serum by 16% (a decrease was observed in 21/25 treated patients, P= 0.0008) (Fig. 3C).
Affiliation: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.