Linked Life Data

12764058

Source:http://linkedlifedata.com/resource/pubmed/id/12764058

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 6
pubmed:dateCreated
2003-5-23
pubmed:abstractText
Parenteral administration of interferon (IFN)-beta is one of the currently approved therapies for multiple sclerosis. One characteristic of this disease is the increased production of gelatinase B, also called matrix metalloproteinase (MMP) 9. Gelatinase B is capable of destroying the blood-brain barrier, and of cleaving myelin basic protein into immunodominant and encephalitogenic fragments, thus playing a functional role and being a therapeutic target in multiple sclerosis. Here we demonstrate that gelatinase B proteolytically cleaves IFN-beta, kills its activity, and hence counteracts this cytokine as an antiviral and immunotherapeutic agent. This proteolysis is more pronounced with IFN-beta-1b than with IFN-beta-1a. Furthermore, the tetracycline minocycline, which has a known blocking effect in experimental autoimmune encephalomyelitis, an in vivo model of acute inflammation in multiple sclerosis, and other MMP inhibitors prevent the in vitro degradation of IFN-beta by gelatinase B. These data provide a novel mechanism and rationale for the inhibition of gelatinase B in diseases in which IFN-beta has a beneficial effect. The combination of gelatinase B inhibitors with better and lower pharmacological formulations of IFN-beta may reduce the side-effects of treatment with IFN-beta, and is therefore proposed for multiple sclerosis therapy and the immunotherapy of viral infections.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-8950
pubmed:author
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1371-81
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Gelatinase B/matrix metalloproteinase-9 cleaves interferon-beta and is a target for immunotherapy.
pubmed:affiliation
Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't