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Cited by 72Multiple Sclerosis Research StudiesProtease and Inhibitor MechanismsCalpain Protease Function and Regulation

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

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Haves-Zburof, Dana, Paperna, Tamar, Gour-Lavie, Alumit, Mandel, Ilana, Glass-Marmor, Lea, Miller, Ariel·2011·Journal of Cellular and Molecular Medicine
DOI 10.1111/j.1582-4934.2010.01229.xPMC PMC3822953
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Abstract

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. Real-time PCR was employed to compare RNA expression levels in peripheral blood leucocytes (PBLs) and ELISA to determine serum protein levels of MS patients and matched healthy individuals. Cathepsin S RNA was higher in MS patients in the relapse state compared to controls (by 74%, P = 3 × 10(-5), n = 30 versus n = 18) with a similar increase observed in serum (66%, P = 0.002, n = 18 versus n = 20). GC treatment reduced cathepsin S levels in PBL RNA (by 44%, P = 6 × 10(-6), n = 27) and serum proteins (by 27%, P = 1 × 10(-5), n = 26), reduced the serum protein levels of pro-cathepsin B (by 8%, P = 0.0007, n = 23), and in parallel increased the serum levels of their inhibitor cystatin C (by 82%, P = 8 × 10(-6), n = 26). IFN-β therapy significantly elevated the RNA levels (n = 16) of cathepsin B (by 16%, P = 0.03), cystatin B (44%, P = 0.004) and cystatin C (48%, P = 0.011). 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.

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  • CST8 is part of a protein family that inhibits the activity of cathepsins, offering a potential mechanism for its inverse AD association.

    “CST8 is part of a protein family that inhibits the activity of cathepsins77, offering a potential mechanism for its inverse AD association.”

    From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [77]

    The Introduction identifies cystatins B and C as inhibitors of cathepsins, and the Results section on glucocorticoid treatment describes cystatin C as a protease inhibitor. The paper does not identify CST8 as a member of that family or examine its activity; the proposed inverse AD association is the citing authors’ interpretation, not the part directly attached to this citation. Page numbers are unavailable in our copy. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Haves-Zburof, D., Paperna, T., Gour-Lavie, A., Mandel, I., Glass-Marmor, L., & Miller, A.
Affiliations
Technion – Israel Institute of Technology (IL)
Corresponding author
Miller, Ariel
ORCID
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2011-10-24
Volume
15
Issue
11
Pages
2421-2429
ISSN
1582-1838 (ISSN-L)
DOI
10.1111/j.1582-4934.2010.01229.x
PMC
PMC3822953
OpenAlex
W1973703293
Cited by
72
References
0
Citations by year
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FWCI
2.05
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1408 d)
Locations
  • Journal of Cellular and Molecular Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
Keywords
cathepsins, cystatin, multiple sclerosis, cathepsin S, cathepsin B, cystatin C, cystatin B, interferon beta therapy, methylprednisolone, glucocorticoids, relapse, treatment response, serum biomarkers, peripheral blood leukocytes, protease inhibitors, disease activity, antigen processing and presentation, extracellular matrix
MeSH terms
Adolescent, Adult, Cathepsin B, Cathepsins, Female, Humans, Leukocytes, Male, Methylprednisolone, Middle Aged, Multiple Sclerosis, RNA, Messenger, Biomarkers, Interferon-beta, Disease Progression, Cystatin B, Cystatin C

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