Caries induced cytokine network in the odontoblast layer of human teeth.
BACKGROUND
Immunologic responses of the tooth to caries begin with odontoblasts recognizing carious bacteria. Inflammatory propagation eventually leads to tooth pulp necrosis and danger to health. The present study aims to determine cytokine gene expression profiles generated within human teeth in response to dental caries in vivo and to build a mechanistic model of these responses and the downstream signaling network.


RESULTS
We demonstrate profound differential up-regulation of inflammatory genes in the odontoblast layer (ODL) in human teeth with caries in vivo, while the pulp remains largely unchanged. Interleukins, chemokines, and all tested receptors thereof were differentially up-regulated in ODL of carious teeth, well over one hundred-fold for 35 of 84 genes. By interrogating reconstructed protein interaction networks corresponding to the differentially up-regulated genes, we develop the hypothesis that pro-inflammatory cytokines highly expressed in ODL of carious teeth, IL-1β, IL-1α, and TNF-α, carry the converged inflammatory signal. We show that IL1β amplifies antimicrobial peptide production in odontoblasts in vitro 100-fold more than lipopolysaccharide, in a manner matching subsequent in vivo measurements.


CONCLUSIONS
Our data suggest that ODL amplifies bacterial signals dramatically by self-feedback cytokine-chemokine signal-receptor cycling, and signal convergence through IL1R1 and possibly others, to increase defensive capacity including antimicrobial peptide production to protect the tooth and contain the battle against carious bacteria within the dentin.
Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, 513 Parnassus Street, San Francisco, CA 94143, Box 0422, USA. Orapin.Horst@ucsf.edu
Orapin V
OV
Horst
Jeremy A
JA
Horst
Ram
R
Samudrala
Beverly A
BA
Dale
D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D003731:Dental Caries / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D003782:Dental Pulp / Q000276:immunology / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D018448:Models, Immunological; D009804:Odontoblasts / Q000276:immunology* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020011:Protective Agents / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014070:Tooth / Q000276:immunology* / Q000473:pathology*; D014158:Transcription, Genetic
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D018076:DNA, Complementary; D018836:Inflammation Mediators; D020011:Protective Agents; D018121:Receptors, Cytokine
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