Cytokine Expression in Gingival Hyperplasia Induced by Cyclosporine in Mice
Objectives: Drug-induced gingival hyperplasia, due to the side effects of certain medicines such as immunosuppressive agents, anti-epileptic drugs and calcium channel blockers, is distinct from chronic marginal periodontitis, which is caused by an infection of oral bacteria into the gingival sulcus. Cyclosporine A (CsA) is a widely used immunosuppressant with clinical applications ranging from organ transplants to chronic inflammatory diseases.
IL-17 is produced exclusively by activated memory T-cells. IL-17 is a T-cell-derived cytokine that may play an important role in the initiation and maintenance of the proinflammatory response and has a potential role in the etiopathogenesis of periodontal disease.
We have developed a CsA-induced gingival hyperplasia mouse model, and here we examine the expression of cytokines including IL-17 and growth factors in gingival hyperplasia.
Methods: The C57BL/6 mice used in this study were specific-pathogen-free 4-week-old males (n=5). For eight weeks, CsA-induced gingival hyperplasia mice received CsA (Sandimmun®, Novartis Pharma) intraperitoneally five times a week (40 mg/kg body weight). Control mice received saline intraperitoneally five times a week. The mice were killed by anesthesia, and the mandibular halves were dissected. They were stained with hematoxylin and eosin (HE). The expression of IL-17, IL-6, EGF and TGF-b mRNA in gingival tissue was determined by real-time RT-PCR.
Results: Thickening of the mucous membrane epithelium was determined by HE staining in CsA-induced gingival hyperplasia mice. The IL-6 and EGF mRNA levels in CsA-induced gingival hyperplasia mice were significantly higher than in control mice. However, IL-17 and TGF-b mRNA levels in CsA-induced gingival hyperplasia mice were not significantly higher than in control mice.
Conclusion: These results suggest that IL-6 and EGF play important roles in the pathogenesis of gingival hyperplasia, but IL-17 and TGF-b do not.
Refrence:
1) Meller, T., Rumjanek, M., et al.: Oral mucosa alterations induced by cyclosporin in mice: morphological features. J. Periodont. Res., 37: 412-415, 2002.
2) Mandy, M. Kristian, B. , et al.: TGF-b and IL-6 drive the production of IL-17 and IL-10 by T cell and restainTh-17 cell-mediated pathology. Nature immunology., 8: 1390-1397, 2007.