Caries induced cytokine network in the odontoblast layer of human teeth.

Orapin V Horst,Beverly A Dale,Jeremy A Horst,Ram Samudrala

doi:10.1186/1471-2172-12-9

Orapin V Horst, Beverly A Dale + Show 2 more

Open Access

https://doi.org/10.1186/1471-2172-12-9

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Abstract

BackgroundImmunologic 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.ResultsWe 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.ConclusionsOur 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.

Highlights

Immunologic responses of the tooth to caries begin with odontoblasts recognizing carious bacteria
In this study we aim to characterize cytokine expression profiles generated within human teeth in response to dental caries in vivo, and to build a mechanistic model of these responses by mapping the in vivo differential gene expression of odontoblast layer (ODL) and pulp in healthy and diseased teeth across known protein interactions
The most abundantly expressed genes in ODL and pulp of normal teeth were cytokine receptor interleukin 1 receptor 1 (IL1R1), C-X-C family chemokine ligand 12 (CXCL12), CXCL14, and macrophage migration inhibitory factor (MIF). These genes were detected by realtime quantitative PCR before 25 amplification cycles, which indicates more abundant expression than other genes detected at the greater amplification cycles

Summary

Introduction

Immunologic responses of the tooth to caries begin with odontoblasts recognizing carious bacteria. 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. Our group and others showed that odontoblasts can mediate host inflammatory responses to caries directly through production of antimicrobial peptides and cytokines, and indirectly through activation of migratory immune cells using in vitro and ex vivo models [10,13,14,15,18,19,20]. In this study we aim to characterize cytokine expression profiles generated within human teeth in response to dental caries in vivo, and to build a mechanistic model of these responses by mapping the in vivo differential gene expression of ODL and pulp in healthy (intact) and diseased (carious) teeth across known protein interactions

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