Cytokine Expression in Gingival Hyperplasia Induced by Cyclosporine in Mice

Fumishige Oseko DDS, PhD, Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Toshiro Yamamoto D.D.S., Ph.D., Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Hiroaki Ichioka DDS, Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Tetsuya Adachi DDS, PhD, Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Masaru Nishigaki DDS, Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Takeshi Amemiya DDS, PhD, Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Narisato Kanamura DDS, PhD, Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

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.

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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.