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- Title
Pre-exposure to high glucose augments lipopolysaccharide-stimulated matrix metalloproteinase-1 expression by human U937 histiocytes.
- Authors
Maldonado, Alejandro; He, Lin; Game, Bryan A.; Nareika, Alena; Sanders, John J.; London, Steve D; Lopes‐Virella, Maria F.; Huang, Yan
- Abstract
Maldonado A, He L, Game BA, Nareika A, Sanders JJ, London SD, Lopes-Virella MF, Huang Y. Pre-exposure to high glucose augments lipopolysaccharide-stimulated matrix metalloproteinase-1 expression by human U937 histiocytes. J Periodont Res 2004; doi: 10.1111/j.1600-0765.2004.00756.x© Blackwell Munksgaard 2004It 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.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 factorκB (NFκB) and mitogen-activated protein kinase (MAPK) cascades.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 NFκB and MAPK signaling pathways. This study has thus delineated a pathogenic mechanism that may be involved in the exacerbated periodontal disease in diabetic patients.
- Subjects
ENDOTOXINS; METALLOPROTEINASES; MACROPHAGES; PERIODONTAL disease; MEDICAL experimentation on humans; MESSENGER RNA
- Publication
Journal of Periodontal Research, 2004, Vol 39, Issue 6, p415
- ISSN
0022-3484
- Publication type
Article
- DOI
10.1111/j.1600-0765.2004.00756.x