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Quintessence Publishing: Journals: QI
Quintessence International

Edited by Eli Eliav

ISSN 0033-6572 (print) • ISSN 1936-7163 (online)

Publication:
November/December 2009
Volume 40 , Issue 10

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Activation of Cyclic AMP Response Element-Binding Protein (CREB) in Aggressive Periodontal Disease

Rainer Buchmann, Dr Med Dent, PD/Ralf Roessler, Dr Med Dent/Anton Sculean, Prof Dr Med Dent

Pages: 857863
PMID: 19898718

Objectives: To report a novel observation of neutrophil signal transduction abnormalities in patients with localized aggressive periodontitis (LAP) that are associated with an enhanced phosphorylation of the nuclear signal transduction protein cyclic AMP response element-binding factor (CREB). Method and Materials: Peripheral venous blood neutrophils of 18 subjects, 9 patients with LAP and 9 race-, sex-, and age-matched healthy controls, were isolated and prepared using the Ficoll-Hypaque density-gradient technique. Neutrophils (5.4 3 106/mL) were stimulated with the chemoattractant FMLP (106 mol/L) for 5 minutes and lysed. Aliquots of these samples were separated by SDS-PAGE (60 g/lane) on 9.0% (w/v) polyacrylamide slab gels and transferred electrophoretically to polyvinyl difluoride membranes. The cell lysates were immunoblotted with a 1:1,000 dilution of rabbit-phospho-CREB antibody that recognizes only the phosphorylated form of CREB at Ser133. The activated CREB was visualized with a luminol-enhanced chemoluminescence detection system and evaluated by laser densitometry. Results: In patients with LAP, the average activation of CREB displayed an overexpression for the unstimulated peripheral blood neutrophils of 80.3% (17.5-fold) compared to healthy controls (4.6%). Conclusion: LAP neutrophils who express their phenotype appear to be constitutively primed, as evidenced by activated CREB in resting cells compared to normal individuals. The genetically primed neutrophil phenotype may contribute to neutrophil-mediated tissue damage in the pathogenesis of LAP. (Quintessence Int 2009;40:857863)

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