Activity, but not mRNA expression of gelatinases correlates with susceptibility to experimental autoimmune encephalomyelitis
2015
Authors:
Petković, FilipŽivanović, Jasmina
Blaževski, Jana
Timotijević, G.
Momčilović, Miljana
Stanojević, Ž.
Stamenković, V.
Milošević, Verica
Stojković, M. Mostarica
Miljković, Đorđe
Document Type:
Article (Published version)
,
© 2015 IBRO. Published by Elsevier Ltd.
Metadata
Show full item recordAbstract:
Experimental autoimmune encephalomyelitis (EAE) is a model of multiple
sclerosis (MS), inflammatory, demyelinating and neurodegenerative
disease of the central nervous system (CNS). Clinically manifested EAE
can be induced in Dark Agouti (DA) rats, but not in Albino Oxford (AO)
rats by immunization with spinal cord homogenate (SCH) and complete
Freund's adjuvant (CFA). Matrix metalloproteinases (MMP) play important
roles in various steps of MS and EAE pathogenesis. Expression of
gelatinases MMP2 and MMP9, their activator MMP14 and their inhibitor
tissue inhibitor of MMP (TIMP) 1 in the CNS of AO and DA rats immunized
with SCH + CFA was determined. Expression of mRNA for MMP2, MMP9 and
MMP14 was higher and expression of TIMP1 mRNA was lower in AO rats.
However, gelatinase activity in spinal cords was higher in samples
obtained from DA rats. Further, while there was no strain difference in
MMP2 and MMP9 mRNA expression in lymph nodes of the immunized rats,
gelatinase activity was higher in DA rats. This activity was reduced by
antiinflammatory cytokines interleukin (IL)-10 and IL-4. Interestingly,
gelatinase activity was detected in the nuclei of cells within the CNS,
but not of those in lymph nodes. Our results imply that
posttranscriptional regulation of MMP2 and MMP9 expression and/or
function determines low gelatinase activity within the CNS and in immune
cells of EAE-resistant AO rats. (C) 2015 IBRO. Published by Elsevier
Ltd. All rights reserved.
Keywords:
matrix metalloproteinase; gelatinase; neuroinflammation; experimental autoimmune encephalomyelitis; ratSource:
Neuroscience, 2015, 292, 1-12Funding / projects:
- Cellular and molecular mechanisms of recovery of rats from experimental autoimmune encephalomyelitis (RS-MESTD-Basic Research (BR or ON)-173035)
- Immunopathogenic and regulatory mechanisms in autoimmune diseases and chronic inflamation (RS-MESTD-Basic Research (BR or ON)-175038)
- Molecular mechanisms of physiological and pharmacological control of inflammation and cancer (RS-MESTD-Basic Research (BR or ON)-173013)
DOI: 10.1016/j.neuroscience.2015.02.015
ISSN: 1873-7544