Pre-exposure to high glucose augments lipopolysaccharide-stimulated matrix metalloproteinase-1 expression by human U937 histiocytes.
OBJECTIVE
It has been well established that patients with diabetes have increased prevalence and severity of periodontal diseases. However, the underlying mechanisms are not well understood. Given that bacterial infection is the primary cause of periodontal disease, we postulated that hyperglycemia may interplay with bacterial virulence factors such as lipopolysaccharide to up-regulate matrix metalloproteinase (MMP), leading to increased periodontal tissue destruction.


RESULTS
We showed that prolonged pre-exposure of U937 histiocytes to high glucose markedly increased lipopolysaccharide-stimulated MMP-1 secretion and mRNA expression. Our results also showed that the effect of high glucose on lipopolysaccharide-induced MMP-1 expression is cell type-specific because no similar response was observed in human gingival fibroblasts. In addition to MMP-1, high glucose also augments lipopolysaccharide-stimulated MMP-7, -8, and -9 mRNA expression. In the investigation of the signaling pathways involved in the enhancement of lipopolysaccharide-induced MMP-1 expression by high glucose, we found that both high glucose and lipopolysaccharide regulate MMP-1 expression through the nuclear factor kappaB (NFkappaB) and mitogen-activated protein kinase (MAPK) cascades.


CONCLUSIONS
The present study has shown that pre-exposure to high glucose and subsequent lipopolysaccharide treatment synergistically stimulates MMP-1 expression by mononuclear phagocytes through the NFkappaB and MAPK signaling pathways. This study has thus delineated a pathogenic mechanism that may be involved in the exacerbated periodontal disease in diabetic patients.
Maldonado
Alejandro
A
Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, USA.
He
Lin
L
Game
Bryan A
BA
Nareika
Alena
A
Sanders
John J
JJ
London
Steve D
SD
Lopes-Virella
Maria F
MF
Huang
Yan
Y
D005947:Glucose / Q000009:adverse effects*; D006644:Histiocytes / Q000201:enzymology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010510:Periodontal Diseases / Q000201:enzymology / Q000209:etiology*; D010586:Phagocytes / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D020298:U937 Cells
D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D020781:Matrix Metalloproteinase 1; D005947:Glucose