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Transcriptional activation of MMP-13 by periodontal pathogenic LPS requires p38 MAP kinaseDepartment of Diagnosis and Surgery, School of Dentistry at Araraquara, State University of Sao Paulo (UNESP), Araraquara, SP, Brazil, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
Department of Oral Biology, State University of New York at Buffalo, Buffalo, New York, USA
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA, klkirk{at}umich.edu, Department of Oral Biology, State University of New York at Buffalo, Buffalo, New York, USA Matrix metalloprotease-13 (MMP-13) is induced by pro-inflammatory cytokines and increased expression is associated with a number of pathological conditions such as tumor metastasis, osteoarthritis, rheumatoid arthritis and periodontal diseases. MMP-13 gene regulation and the signal transduction pathways activated in response to bacterial LPS are largely unknown. In these studies, the role of the mitogen-activated protein kinase (MAPK) pathways in the regulation of MMP-13 induced by lipopolysaccharide was investigated. Lipopolysaccharide from Escherichia coli and Actinobacillus actinomycetemcomitans significantly (P < 0.05) increased MMP-13 steady-state mRNA (average of 27% and 46% increase, respectively) in murine periodontal ligament fibroblasts. MMP-13 mRNA induction was significantly reduced by inhibition of p38 MAP kinase. Immunoblot analysis indicated that p38 signaling was required for LPS-induced MMP-13 expression. Lipopolysaccharide induced proximal promoter reporter (660/+32 mMMP-13) gene activity required p38 signaling. Collectively, these results indicate that lipopolysaccharide-induced murine MMP-13 is regulated by p38 signaling through a transcriptional mechanism.
Key Words: Matrix metalloproteases MMP-13 lipopolysaccharide signal transduction periodontal diseases
Journal of Endotoxin Research, Vol. 13, No. 2,
85-93 (2007) |
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