1995 Fiscal Year Final Research Report Summary
Suppression of group A streptococcal cell wall-induced periodontitis in the rat by an inhibitor of nitric oxide synthase
Project/Area Number |
06671924
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Conservative dentistry
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Research Institution | Maikai University |
Principal Investigator |
IEDA Katsumi Meikai Univ., Sch.of Dentistry, Professor, 歯学部, 教授 (50049350)
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Co-Investigator(Kenkyū-buntansha) |
ICHIMURA Koh Meikai Univ., Sch.of Dentistry, Assistant, 歯学部, 助手 (00232413)
SHIMOJIMA Takahiro Meikai Univ., Sch.of Dentistry, Lecturer, 歯学部, 講師 (60146230)
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Project Period (FY) |
1994 – 1995
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Keywords | Periodontal disease / Nitric oxide / inducible-NOS(iNOS) / NOS inhibitor |
Research Abstract |
Nitric oxide (NO), a toxic radical gas produced during the mechanism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) into rat gingival tissues resulted in self-limiting inflammatory lesions that reached a peak in 2 to 3 days and resolved by 5 to 7 days. An early polymorphonuclear leukocyte response was replaced by a mononuclear infiltrate characterized by a predominance of macrophages. We showed here that NO production is elevated in the inflamed gingiva of SCW-treated rats. Administration of N^G-monomethyl-L-arginine (NMMA), an inhibitor of NOS,profoundly reduced the gingival inflammation. Moreover, NMMA decreased the rise in inflammed gingiva excretion of NO_2^-/NO_3^-, a stable breakdown products of NO,by about 30 to 50%, however, iNOS mRNA was increased about 2-fold in those rats receiving NMMA.Rat neutrophils released NO_2^-/NO_3^- at rate of 12-18 nmols/2*10^6 cells when incubated with A.a LPS.On the other hand, human neutrophils incubated with superoxide disumutase, but not LPS,at 37゚C produced NO_2^-/NO_3^- at a rate of 2.4nmols/2*10^6cell/30min. Human gingival fibroblasts did not release measurable NO_2^-/NO_3^- in response to LPS stimulation, but they induced stromelysin and collagenase activity upon incubation with IL-1 beta. Furthermore, they did release substaitial amounts of PGE_2 from endogenous and exogenous arachidonic acid in the IL-1 beta, and the NO donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP) increased both metalloproteases activity and cyclooxygenase activity in the IL-1 beta. These date provide evidence that NO plays a role in the modulation of metal-dependent proteolytic enzymes or cyclooxygenase pathway which are activated during inflammatory reactions.
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