| 1617 Early Transcriptional Response of Myeloid-Inflammatory Cells to Porphyromonas gingivalis-Lipopolysaccharide (PgLPS) | ||
|
S. NARES1, N. MOUTSOPOULOS2, Z.G. RANGEL3, N. ANGELOV4, P.J. MUNSON5, and S.M. WAHL2, 1UNC at Chapel Hill, Department of Periodontology, NC, USA, 2National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA, 3Analytical Biostatistics Section, Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, NIH, Center for Information Technology, Bethesda, MD, USA, 4Loma Linda University, Department of Periodontics, CA, USA, 5Analytical Biostatistics Section, Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Bethesda, MD, USA Monocytes, macrophages and dendritic cells are TLR+, antigen-presenting cells (APCs) derived from a common lineage that play key roles in innate and adaptive immune responses. Objective: We hypothesized that these cells would express both convergent and divergent functional genomic profiles when exposed to PgLPS and that these transcriptional signatures would provide insight into the complex, initial inflammatory response to microbial challenge linked to periodontal disease. Methods: APCs from individual donors were cultured in media with or without 100ng/ml PgLPS for 1 hour and the early gene expression profiles monitored using Affymetrix Plus 2.0 microarrays. A blocked, 2-way nested ANOVA was applied and the p-value for treatment within cell type calculated for each of the 54,675 ProbeSets. 426 ProbeSets (approximately 237 genes, <1% False Discovery Rate, ³2-fold ± change) were selected and linked to Gene Ontology annotations. Hierarchical cluster analysis was used to cluster the log-fold change relative to control within each cell type. Validation of array results was performed using real-time PCR. Results: Dendritic cells were most transcriptionally responsive to PgLPS followed by monocytes and macrophages. Interestingly, monocytes were more similar to dendritic cells in their transcriptional response than to macrophages. Cell-specific responses were identified together with a transcriptional 'core' response consisting of 115 annotated genes and 27 ESTs. Along with the identification of well characterized LPS-inducible transcripts, uncharacterized genes and genes not previously associated with a PgLPS response in APCs including genes associated with signal transduction (RIP2K, DUSP2) were identified. Conclusions: The existence of this aggregate response may reflect a convergence of PgLPS-regulated biological pathways essential to host defense in APCs. These findings may help to better understand the initial response of inflammatory cells to this periodontal pathogen and identify novel targets amenable to therapeutic intervention. This study was supported by the Division of Intramural Research, NIDCR-NIH and CIT-NIH. | ||
| Seq #188 - Microbial Virulence and Host Responses 9:00 AM-10:30 AM, Saturday, 11 March 2006 Dolphin Hotel So. Hemis IV | ||
|
Back to the Periodontal Research - Pathogenesis Program
| ||