Osteopontin levels and increased disease activity in relapsing–remitting multiple sclerosis patients

Vogt, Monica; Floris, Sarah; Killestein, Joep; Knol, Dirk L.; Smits, M.; Barkhof, Frederik; Polman, CH; Nagelkerken, Lex

doi:10.1016/j.jneuroim.2004.06.007

Cited by 80 publications

(67 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…15,16 However, there is little evidence for a genetic link between OPN and MS disease susceptibility and disease course. 11,13,[17][18][19][20] Elevated OPN levels have also been documented by immunohistochemistry around MS lesions 21,22 although this was not observed by others. 23 The role that OPN plays in EAE and MS remains uncertain, but a prevailing view is that OPN plays a destructive role during EAE since it reduces apoptosis of effector T cells and because the exogenous administration of recombinant OPN exacerbates EAE clinical disease.…”

mentioning

confidence: 90%

See 1 more Smart Citation

Cleavage of Osteopontin by Matrix Metalloproteinase-12 Modulates Experimental Autoimmune Encephalomyelitis Disease in C57BL/6 Mice

DaSilva

Liaw

Yong

2010

The American Journal of Pathology

View full text Add to dashboard Cite

A role for osteopontin (OPN) in promoting disease activity of multiple sclerosis or its animal model experimental autoimmune encephalomyelitis (EAE) has recently been suggested. As the biological activity of OPN is heavily influenced by posttranslational processing, we investigated the capacity of matrix metalloproteinase (MMP)-12 to cleave OPN and determined whether this influenced disease activity. We found that OPN mRNA and protein expression in the spinal cord increased with EAE disease in C57BL/6 mice concurrently with MMP-12 expression. A Western blot of EAE and control spinal cords revealed different OPNimmunoreactive bands, with a pattern that was similar to MMP-12 cleavage of recombinant OPN in vitro. In addition, OPN fragments in the spinal cord of EAEafflicted mice were reduced in MMP-12 ؊/؊ mice compared with wild-type controls. However, examination of OPN ؊/؊ mice in short-and long-term experiments revealed no difference in EAE outcomes from wildtype animals. OPN/MMP-12 double null mice were generated, and it was revealed that MMP-12 ؊/؊ mice had a worsening of disease compared with wild-type mice, which returned to wild-type levels in the OPN/ MMP-12 double null mice. These results suggest that EAE disease activity may be modulated by the cleavage of OPN by

show abstract

mentioning

confidence: 90%

“…Increased levels of OPN protein is reported in the serum and plasma in patients with relapsing-remitting MS compared with controls, [11][12][13][14] particularly during relapses, and in their cerebrospinal fluid. 15,16 However, there is little evidence for a genetic link between OPN and MS disease susceptibility and disease course.…”

mentioning

confidence: 99%

Cleavage of Osteopontin by Matrix Metalloproteinase-12 Modulates Experimental Autoimmune Encephalomyelitis Disease in C57BL/6 Mice

DaSilva

Liaw

Yong

2010

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Further characterization by the same investigators revealed that OPN plays a critical role in the induction and disease process of EAE, an animal model for MS, when they compared WT with OPN gene knockout mice [14]. More recently, studies have confirmed that serum levels of OPN appear elevated in patients with MS as compared with controls [15][16][17], raising the possibility that the phenomenon may be attributable to inflammatory processes in MS. However, although the properties of OPN as a pro-inflammatory cytokine are known, the exact mechanism underlying the role of OPN in CNS inflammation in MS remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Regulatory effects of IFN‐β on production of osteopontin and IL‐17 by CD4⁺ T Cells in MS

Chen

Nie

et al. 2009

Eur J Immunol

View full text Add to dashboard Cite

IFN-b currently serves as one of the major treatments for MS. Its anti-inflammatory mechanism has been reported as involving a shift in cytokine balance from Th1 to Th2 in the T-cell response against elements of the myelin sheath. In addition to the Th1 and Th2 groups, two other important pro-inflammatory cytokines, IL-17 and osteopontin (OPN), are believed to play important roles in CNS inflammation in the pathogenesis of MS. In this study, we examined the potential effects of IFN-b on the regulation of OPN and IL-17 in MS patients. We found that IFN-b used in vitro at 0.5-3 ng/mL significantly inhibited the production of OPN in primary T cells derived from PBMC. The inhibition of OPN was determined to occur at the CD4 1 T-cell level. In addition, IFN-b inhibited the production of IL-17 and IL-21 in CD4 1 T cells. It has been described that IFN-b suppresses IL-17 production through the inhibition of a monocytic cytokine, the intracellular translational isoform of OPN. Our further investigation demonstrated that IFN-b also acted directly on the CD4 1 T cells to regulate OPN and IL-17 expression through the type I IFN receptor-mediated activation of STAT1 and suppression of STAT3 activity. Administration of IFN-b to EAE mice ameliorated the disease severity. Furthermore, spinal cord infiltration of OPN 1 and IL-17 1 cells decreased in IFN-b-treated EAE mice along with decreases in serum levels of OPN and IL-21. Importantly, decreased OPN production by IFN-b treatment contributes to the reduced migratory activity of T cells. Taken together, the results from both in vitro and in vivo experiments indicate that IFN-b treatment can down-regulate the OPN and IL-17 production in MS. This study provides new insights into the mechanism of action of IFN-b in the treatment of MS. IntroductionMS is a disease of the CNS characterized by chronic inflammatory and demyelinating processes [1]. CNS inflammation is considered as an important feature in MS pathology, and is directly associated with the disease process in MS [2]. Agents that have anti-inflammatory properties have been shown to suppress the disease activity to various degrees. MS is now commonly treated with an immunomodulatory agent, IFN-b, which has shown significant treatment efficacy and is Ã These authors contributed equally to the work. Eur. J. Immunol. 2009. 39: 2525-2536 Immunomodulation 2525 thought to involve a number of different mechanisms of action [3,4]. However, despite extensive clinical experience in the use of IFN-b, its mechanism of action has not been fully elucidated. Studies into its mechanism of action have revealed that anti-inflammatory properties of IFN-b function through the regulation of Th1 and Th2 cytokines [5,6]. Further, there is an evidence indicating that IFN-b promotes the production of IL-10 and inhibits the action of pro-inflammatory cytokines [7,8].Osteopontin (OPN), also known as early T lymphocyte activation-1, has been recently recognized as a pro-inflammatory cytokine promoting the production of IFN-g and IL-12 in macrophages...

show abstract

“…In the brain OPN is intimately associated with the extracellular matrix (ECM) and its expression is developmentally regulated, suggesting that it may facilitate neuronal or glial cell migration [12,29]. Consistent with its role in the stress response, OPN has been implicated as a possible mediator of CNS inflammatory diseases, as a neuroprotective agent in acute stroke and is up-regulated in models of CNS degenerative disease and epilepsy [6,22,35].…”

Section: Introductionmentioning

confidence: 99%

Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal

et al. 2007

View full text Add to dashboard Cite

Osteopontin (OPN) is a pleotrophic molecule that has been associated with multiple disorders of the central nervous system (CNS). Its roles in CNS malignancy are unclear but suggest that higher levels of OPN expression correlate with increased tumor grade and increased migratory capacity of tumor cells. In this study OPN cDNA was cloned into a retroviral vector and used to infect F98 Fischer rat-derived glioma cells and U87 human-derived glioblastoma multiforme (GBM) cells in vitro. Cells expressing high levels of OPN migrated less distance than control cells in vitro. This

show abstract

Osteopontin levels and increased disease activity in relapsing–remitting multiple sclerosis patients

Cited by 80 publications

References 25 publications

Cleavage of Osteopontin by Matrix Metalloproteinase-12 Modulates Experimental Autoimmune Encephalomyelitis Disease in C57BL/6 Mice

Cleavage of Osteopontin by Matrix Metalloproteinase-12 Modulates Experimental Autoimmune Encephalomyelitis Disease in C57BL/6 Mice

Regulatory effects of IFN‐β on production of osteopontin and IL‐17 by CD4⁺ T Cells in MS

Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal

Contact Info

Product

Resources

About

Osteopontin levels and increased disease activity in relapsing–remitting multiple sclerosis patients

Cited by 80 publications

References 25 publications

Cleavage of Osteopontin by Matrix Metalloproteinase-12 Modulates Experimental Autoimmune Encephalomyelitis Disease in C57BL/6 Mice

Cleavage of Osteopontin by Matrix Metalloproteinase-12 Modulates Experimental Autoimmune Encephalomyelitis Disease in C57BL/6 Mice

Regulatory effects of IFN‐β on production of osteopontin and IL‐17 by CD4+ T Cells in MS

Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal

Contact Info

Product

Resources

About

Regulatory effects of IFN‐β on production of osteopontin and IL‐17 by CD4⁺ T Cells in MS