J Korean Acad Conserv Dent.  2006 May;31(3):203-214. 10.5395/JKACD.2006.31.3.203.

Anti-inflammatory effects of PPARgamma on human dental pulp cells

• Kim JH

• KMID: 2175820
• DOI: http://doi.org/10.5395/JKACD.2006.31.3.203

Abstract

Dental pulp is a loose, mesenchymal tissue almost entirely enclosed in the dentin. It consists of cells, ground substance, and neural and vascular supplies. Damage to the dental pulp by mechanical, chemical, thermal, and microbial irritants can provoke various types of inflammatory response. Pulpal inflammation leads to the tissue degradation, which is mediated in part by Matrix metalloproteinase leads to accelerate extracellular matrix degradation with pathological pathway. We have now investigated the induction of MMPs and inflammatory cytokines by Lipopolysaccharide (LPS) control of inflammatory mediators by peroxisome proliferator-activated receptors (PPARs). Human dental pulp cells exposed to various concentrations of LPS (1-10 microg/ml) revealed elevated levels of MMP-2 and MMP-9 at 24 hrs of culture. LPS also stimulated the production of ICAM-1, VCAM-1, IL-1beta, and TNF-alpha. Adenovirus PPARgamma (Ad/PPARgamma) and PPARgamma agonist rosiglitazone reduced the synthesis of MMPs, adhesion molecules and pro-inflammatory cytokines. The inhibitory effect of Ad/PPARgamma was higher than that of PPARgamma agonist. These result offer new insights in regard to the anti-inflammatory potential of PPARgamma in human dental pulp cell.

Keyword

Inflammation; MMPs; Adhesion molecules; PPAR; Pulp cell

MeSH Terms

Adenoviridae
Cytokines
Dental Pulp*
Dentin
Equipment and Supplies
Extracellular Matrix
Humans*
Inflammation
Intercellular Adhesion Molecule-1
Irritants
Matrix Metalloproteinases
Peroxisome Proliferator-Activated Receptors
PPAR gamma*
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1
Cytokines
Intercellular Adhesion Molecule-1
Irritants
Matrix Metalloproteinases
PPAR gamma
Peroxisome Proliferator-Activated Receptors
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1

Figure

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  Figure 1 Activation of MMPs secretion in the dental pulp cells treated with LPS for 24 hours. Condition medium were analyzed by gelatin zymography.

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  Figure 2 Activation of cell adhesion molecules in the dental pulp cells were treated with LPS for 24 hours. Western blot analysis detected adhesion molecules (left), Protein bands were quantified by densitometry (right) (A). Modulation of PPARγ in the dental pulp cells treated with LPS for 24 hours (B). Actin was used as a control for protein loading.

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  Figure 3 Down-regulation of adhesion molecules by PPARγ in time-dependent manner. Western blot analysis detected adhesion molecules (left), Protein bands were quantified by densitometry (right) (A). PPARγ expression in the dental pulp cells treated with ad/PPARγ (B). Actin was used as a control for protein loading.

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  Figure 4 The short (A) and long (48h) (B) time effects of PPARγ and rosiglitazone on cell adhesion molecules in the dental pulp cells. (A) Down-regulation of ICAM-1 and VCAM-1 in dental pulp cells combined treated with Ad/PPARγ and rosiglitazone. The cells were infected with 100 MOI of Ad/PPARγ for 1 hours, and then treated with LPS and rosiglitazone for 24 hours. The protein expression was detected by immunoblotting with specific antibody (left), and protein bands were quantified by densitometry (right). (B) Down-regulation of ICAM-1 and VCAM-1 in dental pulp cells combined treated with Ad/PPARγ and rosiglitazone.

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  Figure 5 Down-regulation of MMP-2, -9 by treatment of PPARγ and it's agonist. Left panel shows gelatin Zymography for MMP-2, MMP-9 from dental pulp cells. Actin was used as a control for protein loading. Right panel shows relative densitometric units. Data are expressed as mean ± SD of three separate experiments.

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  Figure 6 Effects of PPARγ and PPARγ agonist on NF-κB activation in the dental pulp cells. Left panel shows western blot analysis for NF-κB in nuclear extracts, IκB in cytosol from dental pulp cells. Actin was used as a control for protein loading. Right panel shows relative densitometric units. Data are expressed as mean ± SD of three separate experiments.

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