Suppression of group A streptococcal cell wall-induced periodontitis in the rat by an inhibitor of nitric oxide synthase

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 06671924
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Conservative dentistry
• Research Institution: Maikai University
• Principal Investigator: IEDA Katsumi Meikai Univ., Sch.of Dentistry, Professor, 歯学部, 教授 (50049350)
• 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)
• Project Period (FY): 1994 – 1995
• 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.