Open AccessCathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis
Author(s) -
HavesZburof Dana,
Paperna Tamar,
GourLavie Alumit,
Mandel Ilana,
GlassMarmor Lea,
Miller Ariel
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01229.x
Subject(s) - cathepsin b , cathepsin , cystatin , cathepsin s , cathepsin l , cathepsin l1 , cathepsin h , cystatin c , medicine , endocrinology , microbiology and biotechnology , chemistry , biology , enzyme , biochemistry , renal function
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.