title: Pre-exposure to high glucose augments lipopolysaccharide-stimulated matrix metalloproteinase-1 expression by human U937 histiocytes.
abstract: 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.
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Maldonado
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Game
authors.forename: Alena
authors.initials: A
authors.lastname: Nareika
authors.forename: John J
authors.initials: JJ
authors.lastname: Sanders
authors.forename: Steve D
authors.initials: SD
authors.lastname: London
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
mesh_terms: 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
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D020781:Matrix Metalloproteinase 1; D005947:Glucose