Anti-inflammatory effects of PPARγ on human dental pulp cells

Article information

Restor Dent Endod. 2006;31(3):203-214

Publication date (electronic) : 2006 May 31

doi : https://doi.org/10.5395/JKACD.2006.31.3.203

Department of Conservative Dentistry, College of Dentistry, Chonbuk National University, Korea.

Corresponding Author: Jeong-Hee Kim. Department of Conservative Dentistry, College of Dentistry, Chonbuk National University, Geumam-Dong, Deokjin-Gu, Jeonju, Jeonbuk, 561-712, Korea. Tel: 82-63-250-2119, Fax: 82-63-250-2049, endo95@naver.com

Received 2006 January 21; Revised 2006 March 03; Accepted 2006 May 08.

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 µg/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-1β, and TNF-α. Adenovirus PPARγ (Ad/PPARγ) and PPARγ agonist rosiglitazone reduced the synthesis of MMPs, adhesion molecules and pro-inflammatory cytokines. The inhibitory effect of Ad/PPARγ was higher than that of PPARγ agonist.

These result offer new insights in regard to the anti-inflammatory potential of PPARγ in human dental pulp cell.

Keywords: Inflammation; MMPs; Adhesion molecules; PPAR; Pulp cell

References

1. Brandenburg K, Andra J, Muller M, Koch MH, Garidel P. Physicochemical properties of bacterial glycopolymers in relation to bioactivity. Carbohydr Res 2003. 338(23)2477–2489.

2. Birkedal-Hansen H. Role of cytokines and inflammatory mediators in tissue destruction. J Periodontal Res 1993. 28500–510.

3. Simonin MA, Bordji K. PPAR-γ ligands modulate effects of LPS in stimulated rat synovial fibroblasts. Am J Physiol Cell Physiol 2002. 282C125–C133.

4. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003. 92(8)827–839.

5. Naito Y, Yoshikawa T. Role of matrix metalloproteinases in inflammatory bowel disease. Mol Aspects Med 2005. 26379–390.

6. Gusman H, Santana RB, Zehnder M. Matrix metalloproteinase levels and gelatinolytic activity in clinically healthy and inflamed human dental pulps. Eur J Oral Sci 2002. 110(5)353–357.

7. Wang CY, Stashenko P. Kinetics of bone-resorbing activity in developing periapical lesion. J Dent Res 1991. 701362–1366.

8. Zhu X, Subbaraman R, Sano H, Jacobs B, Sano A, Boetticher E, Munoz NM, Leff AR. A surrogate method for assessment of beta(2)-integrin-dependent adhesion of human eosinophils to ICAM-1. J Immunol Methods 2000. 240(1-2)157–164.

9. Sawa Y, Yoshida S, Shibata KI, Suzuki M, Mukaida A. Vascular endothelium of human dental pulp expresses diverse adhesion molecules for leukocyte emigration. Tissue Cell 1998. 30(2)281–291.

10. Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta 1996. 130293–109.

11. Jiang C, Ting AT, Seed B. PPAR-γ agonists inhibits production of monocyte inflammatory cytokines. Nature 1998. 39182–86.

12. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem 2000. 43527–550.

13. Lemberger T, Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol 1996. 12335–363.

14. Panagakos FS, O'Boskey JF Jr, Rodriguez E. Regulation of pulp cell matrix metalloproteinase production by cytokines and lipopolysaccharides. J Endod 1996. 22358–361.

15. Zingarelli B, Cook JA. Peroxisome proliferator-activated receptor-gamma is a new therapeutic target in sepsis and inflammation. Shock 2005. 23(5)393–399.

16. Tjäderhane L. The mechanism of pulpal wound healing. Aust Endod J 2002. 28(2)68–74.

17. Lin SK, Wang CC, Huang S, Lee JJ, Chiang CP, Lan WH, Hong CY. Induction of dental pulp fibroblast matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expression by interleukin-1alpha and tumor necrosis factor-alpha through a prostaglandin-dependent pathway. J Endod 2001. 27185–189.

18. Coil J, Tam E, Waterfield JD. Proinflammatory cytokine profiles in pulp fibroblasts stimulated with lipopolysaccharide and methyl mercaptan. J Endod 2004. 30(2)88–91.

19. Min JK, Kim YM, Kim SW, Kwon MC, Kong YY, Hwang IK, Won MH, Rho J, Kwon YG. TNF-related activation-induced cytokine enhances leukocyte adhesiveness: induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein kinase C-dependent NF-kappaB activation in endothelial cells. J Immunol 2005. 175(1)531–540.

20. Sasaki M, Jorden P, Welbourne T, Minagar A, Joh T, Itoh M, Elrod JW, Alexander JS. Troglitazone, a PPAR-gamma activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-alpha. BMC Physiol 2005. 5(1)3–14.

21. Pasceri V, Wu HD, Willerson JT, Yeh ET. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation 2000. 101(3)235–238.

22. Ward JE, Fernades DJ, Taylor CC, Bonacci JV, Quan L, Stewart AG. The PPARgamma ligand, rosiglitazone, reduces airways hyperresponsiveness in a murine model of allergen-induced inflammation. Pulm Pharmacol Ther 2006. 19(1)39–46.

23. Madianos PN, Bobetsis YA, Kinane DF. Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. J Clin Periodontol 2005. 3257–71.

24. Yang WK, Lee WC, Kim MR, Son HH. MMP and TIMP production in periodontal ligament fibroblasts stimulated by prevotella nigrescens lipopolysaccharide. J Korean Acad Conserv Dent 2005. 30(5)372–384.

25. Park SK, Shon WJ, Lim SS. Effect of Sonicated extracts of Enterococcus feacalis on the production of Matrix Metalloproteinase-8 by human polymorphonuclear neutrophils. J Korean Acad Conserv Dent 2005. 30(2)138–144.

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Figure 1

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

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.

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.

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.

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.

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.