Lipopolysaccharide-binding Protein Inhibits Toll-like Receptor 2 Activation by Lipoteichoic Acid in Human Odontoblast-like Cells

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• 作者：Florence Carrouel ; PhD^&lowast ; ; ^&dagger ; ; Marie-Jeanne Staquet ; PhD^&lowast ; ; Jean-Franç ; ois Keller ; DDS ; PhD^&lowast ; ; ^&dagger ; ; ^&Dagger ; ; Caroline Baudouin ; PhD^§ ; ; Philippe Msika ; PhD^§ ; ; Franç ; oise Bleicher ; PhD^&lowast ; ; ^&dagger ; ; Brigitte Alliot-Licht ; DDS ; PhD^|| ; Jean-Christophe Farges ; DDS ; PhD^&lowast ; ; ^&dagger ; ; ^&Dagger ; ; ^{jean-christophe.farges@univ-lyon1.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CD14 ; CXCL8 ; human dental pulp ; IL-6 ; innate immunity ; LBP ; NF-κB ; pathogen-associated molecular pattern ; p38 ; Toll-like receptor
• 刊名：Journal of Endodontics
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：39
• 期：8
• 页码：1008-1014
• 全文大小：775 K

文摘

Previous studies have suggested that odontoblasts sense gram-positive bacteria components through Toll-like receptor 2 (TLR2) and trigger dental pulp immunity by producing proinflammatory cytokines. Currently, the factors that modulate odontoblast TLR2 activation are unknown. Our aim was to investigate lipopolysaccharide-binding protein (LBP) effects on the TLR2-mediated odontoblast response.

Methods

Human odontoblast-like cells were stimulated with lipoteichoic acid (LTA) (a TLR2 ligand), LBP, CD14 (a TLR2 cofactor), or various combinations of LTA/LBP, LTA/CD14, or LTA/CD14/LBP. CXCL8, IL6, and TLR2 gene expression was assessed by real-time polymerase chain reaction. CXCL8 and interleukin (IL)-6 production was determined by enzyme-linked immunosorbent assay in culture supernatants of cells stimulated with LTA, LTA/CD14, or LTA/CD14/LBP. LBP effects on nuclear factor kappa B (NF-κB), p38, JNK, ERK, STAT3, and p70S6 signaling pathways were determined in LTA-stimulated odontoblast-like cells with a multiplex biometric immunoassay. LBP effects were compared with specific inhibitors of these signaling pathways. LBP transcript and protein were investigated in vivo in healthy and inflamed dental pulps by real-time polymerase chain reaction and immunohistochemistry.

Results

Activation of CXCL8, IL6, and TLR2 gene expression and CXCL8 and IL-6 secretion in LTA- and LTA/CD14-stimulated odontoblast-like cells was significantly decreased by LBP. LBP inhibited NF-κB and p38 signaling pathways in LTA-stimulated cells in a similar way to NF-κB and p38 inhibitors. LBP transcript and protein were detected in vivo in inflamed dental pulps but not in healthy ones.

Conclusions

These results demonstrate that LBP reduces TLR2-dependent production of inflammatory cytokines by odontoblast-like cells. We suggest that in this way it could modulate host defense in human dental pulp.