Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis.
J Cell Mol Med
; 15(11): 2421-9, 2011 Nov.
Article
en En
| MEDLINE
| ID: mdl-21143385
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-ß [IFN-ß] and the glucocorticoid [GC] methylprednisolone), and whether they are associated with the IFN-ß 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-ß 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-ß (16%, P = 0.006, n = 25). Interestingly, pre-treatment serum cathepsin S/cystatin C ratio was higher in 'good responders' to IFN-ß 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-ß therapy, and that these proteins should be further evaluated as biomarkers in MS.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Catepsina B
/
Catepsinas
/
Cistatina B
/
Cistatina C
/
Esclerosis Múltiple
Límite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2011
Tipo del documento:
Article
País de afiliación:
Israel