Sizuo Kitano1,*, Kenji Irimura2, Toru Sasaki1,
Naoko Abe3, Atsuyo Baba3, Yoichiro Miyake4,
Nobuhiko Katunuma5 and Kenji Yamamoto3
1Pharmacology Research Laboratory, 2Drug Safety
Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co.,
Ltd., 224-2, Ebisuo, Hiraishi,Kawauchi-cho, Tokushima 771-0194, Japan
3Department of Pharmacology, Faculty of Dentistry, Kyushu University,
Higashi-ku, Fukuoka 812-8582, Japan
4Department of Microbiology, Tokushima University School of Dentistry,
3-18-15, Kuramoto-cho, Tokushima 770-8504, Japan
5Institute for Health Sciences, Tokushima Bunri University, 180,
Bouji, Nisihama, Yamashiro-cho, Tokushima 770-8514, Japan
*Corresponding author. FAX: +81-88-665-6554
E-mail: shi-kitano@taiho.co.jp
Abstract: In this study, we developed a procedure to produce gingivitis
in rats by inoculation of Porphyromonas gingivalis and studied the
contribution of the bacterial cysteine proteinases, Arg-gingipain (Rgp)
and Lys-gingipain (Kgp), to the pathology in the gingiva. To adhere the
bacterium to periodontal tissues, a cotton thread was inserted between the
first and second molar of right maxillary sites of rats. Rats in group A
were administered with vehicle alone after bacterial (strain W83) inoculation.
In group B, the bacteria were inoculated in combination with leupeptin,
a potent inhibitor of Rgp and Kgp, and then leupeptin alone was administered
the week after. Rats in group C were administered leupeptin for 6 weeks
after bacteria inoculation. All left maxillary gingiva in three groups showed
no inflammatory changes. Right maxillary gingiva of group A showed most
of the clinical landmarks of gingivitis. Leupeptin exhibited only a little
inhibitory effect on this gingivitis in group B, whereas it had a strong
inhibitory effect on the inflammation in group C. These results suggest
that P. gingivalis-induced gingivitis is attributable to Rgp and
Kgp and that leupeptin is more effective in the late phase than the early
stage of gingivitis.
Keywords: Arg-gingipain, Lys-gingipain, Gingivitis, Leupeptin, Porphyromonas
gingivalis
Copyright The Japanese Pharmacological Society
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