Linked Life Data

9755853

Source:http://linkedlifedata.com/resource/pubmed/id/9755853

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-10-5
pubmed:abstractText
Matrix metalloproteinase (MMPs) enzymes are implicated in matrix remodelling during proliferative inflammatory processes including wound healing. We report here synergistic upregulation of MMP-9 protein and mRNA by platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF) in combination with interleukin-1alpha (IL-1alpha) or tumour necrosis factor-alpha (TNF-alpha) in primary rabbit and human dermal fibroblasts. The synergistic interaction between growth factors and cytokines implies that basement membrane remodelling is maximal physiologically when both are present together. The signalling pathways mediating this synergistic regulation are not understood, although analysis of the MMP-9 promoter has identified an essential proximal AP-1 element and an upstream nuclear factor kappa-B (NF-kappaB) site. Using electromobility shift assays, binding to the AP-1 site was only slightly increased by growth factors and cytokines. NF-kappaB binding was rapidly induced by IL-1alpha or TNF-alpha but was neither induced nor potentiated by bFGF or PDGF. Neither AP-1 nor NF-kappaB was therefore sufficient on its own for synergistic regulation. Using a recently developed adenovirus that overexpresses the inhibitory subunit, IkappaB alpha, we demonstrated an absolute requirement for NF-kappaB in upregulation of MMP-9. Activation of NF-kappaB binding by inflammatory cytokines was therefore necessary but not sufficient for synergistic upregulation of MMP-9.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-5793
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
435
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappa B.
pubmed:affiliation
Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, UK.
pubmed:publicationType
Journal Article