Suppression of gingival inflammation induced by Porphyromonas gingivalis in rats by leupeptin.
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.
Pharmacology Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., Japan. shi-kitano@taiho.co.jp
S
S
Kitano
K
K
Irimura
T
T
Sasaki
N
N
Abe
A
A
Baba
Y
Y
Miyake
N
N
Katunuma
K
K
Yamamoto
D018829:Adhesins, Bacterial / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D016866:Bacteroidaceae Infections / Q000188:drug therapy / Q000382:microbiology*; D003546:Cysteine Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D000080867:Gingipain Cysteine Endopeptidases; D005891:Gingivitis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D006388:Hemagglutinins / Q000187:drug effects* / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008437:Maxilla / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000472:pathogenicity*; D051381:Rats; D017208:Rats, Wistar; D014774:Virulence
D018829:Adhesins, Bacterial; D015853:Cysteine Proteinase Inhibitors; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D007976:Leupeptins; D003546:Cysteine Endopeptidases; C032854:leupeptin