Linked Life Data

21327328

Source:http://linkedlifedata.com/resource/pubmed/id/21327328

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-3-1
pubmed:abstractText
The adipocytokine visfatin is closely associated with metabolic disorders. This study explored the effects of visfatin on macrophage-induced inflammation in atheroma. The ability of visfatin to enhance extracellular matrix metalloproteinase inducer (EMMPRIN) expression, matrix metalloproteinase-9 (MMP-9) production and enzymatic activity in THP-1 derived macrophages as well as the mechanisms involved were investigated. EMMPRIN and MMP-9 mRNA levels were investigated by RT-PCR. EMMPRIN and MMP-9 protein levels, nuclear factor (NF)-?B -p65 protein levels, peroxisome proliferator-activated receptor ? (PPAR?) protein levels, and mitogen-activated protein kinase (MAPK) phosphorylation were determined by Western blotting. MMP-9 enzymatic activity was assayed by gelatin zymography. Visfatin (50-400 ng/ml) induced EMMPRIN and MMP-9 depending on the dosage used. Visfatin elicited the activation of NF-?B and MAPK (p38, ERK1/2). Exogenous nicotinamide mononucleotide (NMN), the product of nicotinamide phosphoribosyltransferase (NAMPT) activity, mimicked the effects of visfatin on MAPK (p38, ERK1/2)-NF-?B activation and EMMPRIN/MMP-9 induction. Using the p38 inhibitor, SB203580, the ERK1/2 inhibitor PD98059, the NF-?B inhibitor, pyrrolidine dithiocarbamate and the NAMPT inhibitor FK866, we demonstrated that the visfatin pro-inflammatory action was through the NAMPT-MAPK (p38, ERK1/2)-NF-?B pathway. Furthermore, the visfatin pro-inflammatory action was not prevented by insulin receptor blockade or by a PPAR? agonist. Visfatin did not modulate PPAR? expression. Retinoid X receptor (RXR) agonist suppressed the effects of visfatin on EMMPRIN/MMP-9, NF-?B, but not on MAPK activation. In conclusion, we have demonstrated that visfatin enhances atheroma inflammation through the NAMPT-MAPK (p38, ERK1/2)-NF-?B-EMMPRIN/MMP-9 pathway, a key feature of atherosclerotic diseases linked to metabolic disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1791-244X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
607-15
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Visfatin/PBEF/Nampt induces EMMPRIN and MMP-9 production in macrophages via the NAMPT-MAPK (p38, ERK1/2)-NF-?B signaling pathway.
pubmed:affiliation
Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, P.R. China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't