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Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis.

Haves-Zburof D, Paperna T, Gour-Lavie A, Mandel I, Glass-Marmor L, Miller A - J. Cell. Mol. Med. (2011)

Bottom Line: In the serum, only cathepsin S levels were reduced by IFN-β (16%, P = 0.006, n = 25).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).These results suggest that cathepsin S and cystatin C may contribute to disease activity in MS, specifically in a subgroup of patients that are responsive to IFN-β therapy, and that these proteins should be further evaluated as biomarkers in MS.

View Article: PubMed Central - PubMed

Affiliation: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

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IFN-β effects on cathepsins and cystatins expression in PBLs and sera from MS patients in remission. (A) Expression levels of cathepsins and cystatins following a 3–6 month period of IFN-β treatment and relative to pre-treatment levels, quantified by 2−ΔΔCT values; n= 16. (B) Cathepsin S serum protein levels before and following a 3–6 month period of IFN-β treatment were analysed by ELISA (n= 27). (C) Ratios between the serum levels of the proteases and the cystatin C inhibitor. Horizontal bars: median of fold changes of during treatment relative to pre-treatment ratios.
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fig03: IFN-β effects on cathepsins and cystatins expression in PBLs and sera from MS patients in remission. (A) Expression levels of cathepsins and cystatins following a 3–6 month period of IFN-β treatment and relative to pre-treatment levels, quantified by 2−ΔΔCT values; n= 16. (B) Cathepsin S serum protein levels before and following a 3–6 month period of IFN-β treatment were analysed by ELISA (n= 27). (C) Ratios between the serum levels of the proteases and the cystatin C inhibitor. Horizontal bars: median of fold changes of during treatment relative to pre-treatment ratios.

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).


Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis.

Haves-Zburof D, Paperna T, Gour-Lavie A, Mandel I, Glass-Marmor L, Miller A - J. Cell. Mol. Med. (2011)

IFN-β effects on cathepsins and cystatins expression in PBLs and sera from MS patients in remission. (A) Expression levels of cathepsins and cystatins following a 3–6 month period of IFN-β treatment and relative to pre-treatment levels, quantified by 2−ΔΔCT values; n= 16. (B) Cathepsin S serum protein levels before and following a 3–6 month period of IFN-β treatment were analysed by ELISA (n= 27). (C) Ratios between the serum levels of the proteases and the cystatin C inhibitor. Horizontal bars: median of fold changes of during treatment relative to pre-treatment ratios.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822953&req=5

fig03: IFN-β effects on cathepsins and cystatins expression in PBLs and sera from MS patients in remission. (A) Expression levels of cathepsins and cystatins following a 3–6 month period of IFN-β treatment and relative to pre-treatment levels, quantified by 2−ΔΔCT values; n= 16. (B) Cathepsin S serum protein levels before and following a 3–6 month period of IFN-β treatment were analysed by ELISA (n= 27). (C) Ratios between the serum levels of the proteases and the cystatin C inhibitor. Horizontal bars: median of fold changes of during treatment relative to pre-treatment ratios.
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).

Bottom Line: In the serum, only cathepsin S levels were reduced by IFN-β (16%, P = 0.006, n = 25).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).These results suggest that cathepsin S and cystatin C may contribute to disease activity in MS, specifically in a subgroup of patients that are responsive to IFN-β therapy, and that these proteins should be further evaluated as biomarkers in MS.

View Article: PubMed Central - PubMed

Affiliation: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Show MeSH
Related in: MedlinePlus