Linked Life Data

15941782

Source:http://linkedlifedata.com/resource/pubmed/id/15941782

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-9-9
pubmed:abstractText
The plasma lactate concentration in patients with obesity and type 2 diabetes is often higher than that in nondiabetic individuals. Although it is known that increased lactate concentration is an independent risk factor for developing type 2 diabetes, the underlying mechanisms are not well understood. Because inflammation plays an important role in the development of type 2 diabetes, we postulated that increased lactate level might contribute to the pathogenesis of type 2 diabetes by enhancing inflammation. In the present study, we demonstrated that preexposure of U937 macrophage-like cells to sodium lactate increased LPS-stimulated matrix metalloproteinase (MMP)-1, IL-1beta, and IL-6 secretion. Augmentation of LPS-stimulated MMP-1 secretion was diminished when sodium lactate was replaced by lactic acid that reduced pH in the culture medium. Furthermore, quantitative real-time PCR indicated that the increased secretion of MMP-1, IL-1beta, and IL-6 was due to increased mRNA expression. To explore the underlying signaling mechanism, blocking studies using specific inhibitors for NF-kappaB and MAPK cascades were performed. Results showed that blocking of either NF-kappaB or MAPK pathways led to the inhibition of MMP-1, IL-1beta, and IL-6 expression stimulated by sodium lactate, LPS, or both. Finally, electrophoretic mobility shift assays showed a synergy between sodium lactate and LPS on AP-1 and NF-kappaB transcriptional activities. In conclusion, this study has demonstrated for the first time that sodium lactate and LPS exert synergistic effect on MMP and cytokine expression through NF-kappaB and MAPK pathways and revealed a novel mechanism potentially involved in the development of type 2 diabetes and its complications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0193-1849
pubmed:author
pubmed:issnType
Print
pubmed:volume
289
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E534-42
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Sodium lactate increases LPS-stimulated MMP and cytokine expression in U937 histiocytes by enhancing AP-1 and NF-kappaB transcriptional activities.
pubmed:affiliation
Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't