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.
Kitano
S
S
Pharmacology Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., Japan. shi-kitano@taiho.co.jp
Irimura
K
K
Sasaki
T
T
Abe
N
N
Baba
A
A
Miyake
Y
Y
Katunuma
N
N
Yamamoto
K
K
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