SciELO - Scientific Electronic Library Online

 
vol.12 número4Asociación entre microorganismos y la capacidad amortiguadora de la saliva con la caries dental de escolaresEfectos de la mezcla de colágena-PVP, sobre el metabolismo y proliferación celular de fibroblastos gingivales humanos cultivados índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados

Revista

Articulo

Indicadores

Links relacionados

  • No hay artículos similaresSimilares en SciELO

Compartir


Revista odontológica mexicana

versión impresa ISSN 1870-199X

Rev. Odont. Mex vol.12 no.4 Ciudad de México dic. 2008

https://doi.org/10.22201/fo.1870199xp.2008.12.4.15625 

Trabajos originales

Efecto del lipopolisacárido (LPS) y el ácido lipoteicoico (LTA) sobre la ciclooxigenasa2־ (COX-2) en células pulpares humanas

Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) effects on cyclooxygenase-2 in human dental pulp cells

Ana Guadalupe Ontiveros Granados*  ** 

Gloria Gutiérrez Venegas* 

María del Rosario Lazo García* 

*Laboratorio de Bioquímica, DEPeI de la FO. UNAM.


Resumen

Las toxinas bacterianas como el lipopolisacárido (LPS) y el ácido lipoteicoico (LTA), están presentes en bacterias Gram-negativas y Gram-positivas, respectivamente. Éstas originan el proceso inflamatorio pulpar. En este estudio, se investigo el efecto de LTA y LPS sobre la expresión de la enzima ciclooxigenasa-2 en células pulpares humanas. Se partió de la hipótesis de que estas moléculas participan en el proceso inflamatorio pulpar a través de la sintesis de la ciclooxigenasa-2 en células pulpares humanas. Para evaluar esta hipótesis, se estudió el efecto del LPS y el LTA en cultivos primarios de células pulpares humanas. Finalmente, se caracterizaron las vías y moléculas involucradas en la expresión de COX-2. En las células pulpares humanas tratadas con LTA o LPS, se detectó que estas moléculas promueven la expresión de COX-2. Por otro lado se encontró que la expresión de COX-2 se ve bloqueada por tratamientos con SB203580, PD98059 y estaurosporina. Los resultados demostraron que el tratamiento con LTA y LPS promueven la expresión de COX-2 en eventos donde participan las proteínas cinasas p38, ERK y PKC. Los hallazgos son importantes porque COX-2 está involucrada en la síntesis de PGE2, involucrada en el establecimiento de procesos inflamato rios crónicos. Finalmente se caracterizó la naturaleza de un mediador implicado en el proceso de una pulpitis.

Palabras clave: Ácido lipoteicoico; LTA; lipopolisacárido; LPS; ciclooxigenasa; COX-2; prostaglandina E2; PGE2; ERK; proteína cinasa regulada extracelularmente; PKC; proteína cinasa C; JKN cinasa aminoterminal reguladora del factor de transcripción C-Jun; milimolar (mM)

Abstract

Bacterial toxins such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA) can be found in Gram-negative and Gram-positive bacteria, respectively. This toxins cause an inflammatory process denominated pulpitis. In the present study, the effect of LTA and LPS on the expression of cyclooxygenase-2 in human dental pulp cells was investigated. For this study a hypothesis was made, that this molecules take part in the dental pulp inflammatory process through the cyclooxygenase-2 synthesis in human pulp cells. To evaluate this hypothesis the effect of LPS and LTA was studied in primary cultures of human pulp cells. Finally, the pathways and molecules involved in COX-2 expression were characterized. In human dental pulp cells treated with LTA or LPS, it was detected that these molecules promote COX-2 expression. On the other hand, it was founded that the expression of COX-2 in human pulp cells was blocked by treatments with SB203580, PD98059, and Estaurosporine. The results of the present study demonstrate that treatments with LTA and LPS promote COX-2 expression in events related with protein kinase p38, ERK and PKC. The findings of this investigation are important because COX-2 is related to the synthesis of PGE2, which leads to a chronic inflammatory process. Finally, the nature of a mediator implied in the pulpitis process was characterized.

Keywords: LTA; lypoteichoic acid; LPS; lipopolysaccharide; COX-2; cyclooxygenase-2; PGE2; prostaglandin E2; ERK; extracellular signal regulated protein kinases; PKC; protein kinases C; JNK; C-Jun NH2-terminal kinase

Texto completo disponible sólo en PDF.

REFERENCIAS

1. Cohen S, Burns R. Vías de la pulpa. Editorial Elsevier Science. Octava edición. Madrid España. 2002: 405-595. [ Links ]

2. Weine F. Tratamiento endodóntico. Quinta edición. Madrid España. Editorial Harcourt. 2000: 79-134. [ Links ]

3. Love RM, Jenkinson HF. Invasion of dentinal tubules by oral bacteria. Crit Rev Oral Biol Med 2002; 13(2): 171-183. [ Links ]

4. Gutiérrez G, Kawasaki P. Los lipopolisacáridos: Estructura, receptores y transducción de señales. Simposium de Transducción de Señales. Universidad Nacional Autónoma de México. Julio 2002: 31-38. [ Links ]

5. Yang L, Tsai C. Induction of vascular endothelial growth factor expression in human pulp fibroblasts stimulated with black-pigmented Bacteroides. Int Endod Journal 2004; 37: 588-592. [ Links ]

6. Gruber R, Kandier B. Dental pulp fibroblasts contain target cells for lysophosphatidic acid. J Dent Res 2004; 83: 491-495. [ Links ]

7. Telles P, Hanks C. Lipoteichoic acid Up-regulates VEGF expression in macrophages and pulp cells. J Dent Res 2003; 82: 466-470. [ Links ]

8. Tokuda M, Nagaoka S. Substance P enhances expression of lipopolysaccharide-induced inflammatory factors in dental pulp cells. J Endod 2004; 30(11): 770-774. [ Links ]

9. Gruber R, Jindra C. Proliferation of dental pulp fibroblasts in response to thrombin involves mitogen-activated protein kinase signalling. Int Endod Journal 2004; 37: 145-150. [ Links ]

10. lnoki R, Kudo T, Olgart L. Dynamic aspects of dental pulp. Molecular biology, pharmacology and pathophysiology. Champma and Hall. 1st edition. 1990: 51-69, 385-403. [ Links ]

11. Hargreaves KM, Goodis HE. Seltzer and Bender's Dental Pulp. Quintessence Books. 2002: 227-281. [ Links ]

12. Slots J, Taubman M. Contemporary Oral Microbiology and Immunology. Mosby Year Book. 1992: 3-24, 533-560. [ Links ]

13. Sugawara S, Arakaki R et al. Lipoteichoic acid acts as an antagonist and an agonist of lipopolysaccharide on human gingival fibroblasts and monocytes in a CD14-Dependent Manner. Infection and Immunity 1999: 1623-1632. [ Links ]

14. Lin S, Yeng-Ping-Kuo M et al. Differential regulation of inter-leukin-6 and inducible cyclooxygenase gene expression by cytokines trough prostaglandin-depend and-independent mechanisms in human dental pulp fibroblasts. J Endod 2002; 28(3): 197-201. [ Links ]

15. Chao Y, Shun-Fa Y et al. Proinflammatory cytokines induce cyclooxygenase 2 mRNA and protein expression in human pulp cell cultures. J Endod 2003; 29(3): 201-204. [ Links ]

16. Botero T, Shelburne Ch et al. TLR4 mediates LPS-induced VEGF expression in odontoblasts. J Endod 2006; 32(10): 951-955. [ Links ]

17. Su S, Hua K et al. LTA and LPS mediated activation of protein kinases in the regulation of inflammatory cytokines expression In macrophages. Clinica Chimica Acta 2006; 374: 106-115. [ Links ]

18. Lin S, Wang Ch. Induction of dental pulp fibroblast matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 gene expression by interleukin-1a and Tumor Necrosis Factor- a through a prostaglandin-dependent pathway. J Endod 2001; 27(3): 185-189. [ Links ]

19. Kawashima N, Kawanishi H. Effect of NOS inhibitor on cytokine and COX-2 expression in rat pulpitis. J Dent Res 2005; 84(89): 762-767. [ Links ]

20. Jacinto R, Hartung T. Lipopolysaccharide-and Lipoteichoic Acid-induced tolerance and Cross- tolerance: Distinct alterations in IL-1 Receptor-associated kinase. J Immunol 2002; 168: 6136-6141. [ Links ]

21. Chang Y, Lai Ch et al. Stimulation of matrix metalloproteinases by Black-pigmented Bacteroides in human pulp and pe-riodontal ligament cell cultures. J Endod 2002; 28(2): 90-93. [ Links ]

22. Durand S, Flacher V et al. Lipoteichoic acid increases TLR and functional chemokine expression while reducing dentin formation in in vitro differentiated human odontoblasts. J Immuno 2006; 176: 2880-2887. [ Links ]

23. Wu H, Hsieh W et al. Lipoteichoic acid induces prostaglandin E2 release and cyclooxygenase-2 synthesis in rat cortical neuronal cells: Involvement of PKCƐ and ERK activation. Life Sciences 2006; 79: 272-280. [ Links ]

24. Murray P, Smyth T et al. Analysis of pulpar reactions to restorative procedures, materials, pulp capping, and future therapies. Crit Rev Oral Bio Med 2002; 13(6): 509-520. [ Links ]

25. Chávez PL, Svensater G et al. Streptococci from root canal In tete with apical periodontitis receiving endodontic treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005; 100: 232-241. [ Links ]

26. Mitsiadis T. Molecular aspects of tooth pathogenesis and repair in vivo an in vitro models. Adv Dent Res 2001; 15: 59-62. [ Links ]

27. Gutierrez G, Maldonado S. Role of p38 in nitric oxide and ??clooxigenase expression, and nitric oxide and PGE2 synthesis in human gingival fibroblasts stimulated with lipopolysaccharides. Life Sciences 2005; 77: 60-73. [ Links ]

28. Willoughby D, Moore A. COX-1, COX-2 and COX3 and the future treatment of chronic inflammatory disease. The Lancet 2000; 335: 646-648. [ Links ]

**Dirección para correspondencia: Ana Guadalupe Ontiveros Granados. 3a Cerrada de Portoalegre Núm. 24. Col. El Retoño. Deleg. Iztapalapa 09440. México, D.F.. anislu@yahoo.com.mx. 0445541777174

Creative Commons License Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons