| Periapical lesions begin as a bacterial infection in the dental pulp and involves recruitment of inflammatory cells, generation of cytokines, elaboration of lytic enzymes, and activation of osteoclasts, which leads to alveolar bone resorption. The periapical lesion represents an inflammatory and immune response. The host response is complex; it involves both the recruitment of different inflammatory cells and participation of an extensive network of immunologic mechanisms, including cytokine production. CD4+ T-lymphocytes are the predominant inflammatory cells that infiltrate the pathogenesis of periapical lesions, and play a key role in the disease.IL-17 is produced almost exclusively by activated T cells, and is a definitive of a new class of effector T helper cell subsets called "Th17". IL-17 is clearly a proinflammatory cytokine with potent effects on numerous cells. The proinflammatory functions of IL-17 have been examined in many contexts. In vitro, IL-17 has been shown to activate fibroblast, epithelial cells, endothelial cells, and osteoblasts to produce proinflammatory cytokines such as IL-6, IL-8, granulocyte colony-stimulating factor and matrix metalloproteinases. It could also affect osteoclastic bone resportion by stimulating osteoblasts to produce receptor activator of NF-κB (RANKL) that affect the activity and formation of osteoclast. In humans, IL-17 has been associated with the pathology of numerous autoimmune and inflammatory diseases, such as rheumatoid arthritis (RA), systemtic lupus erythematosus, multiple sclerosis, psoriasis, and allograft rejection. The aim of this study is to examine the presence of IL-17 in the periapical lesions of rats and human, and determine the effect of IL-17 on IL-6 and IL-8 production in human periodontal ligament fibroblast.Experiment One: Establishment of induced periapical lesions in ratsObjective:the purpose of this study was to establish the animal model of periapical lesions in rats.Materials and Methods:Thirty-five Sprague-Dawley (SD) rats were randomly divided into 5 groups. All rats were anesthetized, the pulps of the lower first molars were exposed and left open to the oral environment throughout the experiment. Seven rats in each group were sacrificed at 0,7,14,21 and 28 days after lesion induction. The jaws that contain the first molar were obtained and subject to radiological and histological examination.Results:According to the radiological analysis, the periapical shadow could be observed on day 7. From day 7 to 28, the area of periapical shadow was increased in a time-dependent course. According to the histological examination, the periapical region was intact, and neither inflammation nor bone resorption could be observed in the negative controls on day 0. On day 7, a mild infiltration of acute inflammation cells could be observed. Then small areas of periapical alveolar bone resorption occurred. On day 14, signs of inflammation in the periapical tissues and alveolar bone resorption were observed. On day 21, a abscess was seen around the root apex with inflammatory cell infiltration and alveolar bone resorption was found. On day 28, the apical abscess enlarged and alveolar bone resorption was still found.Conclusion:The exposure of rat’s pulp of molar to the oral environment is an efficient way to establish experimental periapical lesions, which may be an ideal animal model to study the pathology of periapical disease.Experiment two: Immunohistochemical localization of IL-17 in experimental apical periodontitis in ratsObjective:The purpose of this study was to investigate the immunohistochemical localization of IL-17 during the development of periapical lesions in rats.Materials and Methods:Periapical lesions developed within 28 days following mandibular first molar pulp exposure in Sprague-Dawley rats. The animals were randomly sacrificed at 0,7,14,21 and 28 days after pulpal exposure. The jaws which contained the first molar were obtained and routinely prepared for immunohistochemistry and enzymehistochemistry.Result:From day 0 to day 28, the number of IL-17-positive cells and neutrophils ascended and peaked on day 28. Osteoclast numbers substantially multiplied from day 0 to day 14 and then gradually decreased from day 14 to day 28. In addition, there was a significant positive correlation between the number of IL-17 positive cell and the area of periapical lesion size, and there was also a significant positive correlation between the number of IL-17 positive cell and neutrophils.Conclusion:These findings demonstrated that IL-17 could be observed, and might possibly be involved in the inflammatory response and bone resorption of periapical tissues as well as associated with periapical lesion pathogenesis.Experiment Three: The potential role and mechanism of IL-17 in human chronic periapical lesionsObjective:The aim of this study was to investigate the presence of IL-17 in the human periapical lesions and study the effect of IL-17 on the PDLC to stimulate the production of IL-6 and IL-8 by using the method of RT-PCR and EILSAMaterials and Methods:Twenty-nine human periapical lesion samples were obtained in the clinic,10 of them were selected for histological and immunohistochemicals to determine the presence of IL-17. Another 19 samples were analyzed using RT-PCR to examine the mRNA expression of IL-17, IL-6 and IL-8. The correlation between the expression of IL-17 and IL-6/IL-8 was also analyzed. The effect of IL-17 on the production of the inflammatory cytokine IL-6 and IL-8 by PDLC was investigated in vitro.Result:The data demonstrated that the amount of IL-17 was present in periapical lesions in levels significantly higher than in healthy subjects. There was a positive correlation between the mRNA levels of IL-17 and IL-8, but not between IL-17 and IL-6. IL-17-stimulated PDLC to produce IL-6 and IL-8 in a dose-and time-dependent fashion.Conclusion:These results indicate that IL-17 produced in the periapical lesions may exacerbate the inflammatory response in part via inflammatory cytokines of IL-6 and IL-8 from PDLC. In addition, this findings have contributes to our understanding of the molecular basis of bone destruction and immunology and further elucidates the pathogenesis of other inflammatory diseases that induce bone resorption. |
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