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Updated: Jun 23, 2026
A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
Chronic ingestion of Porphyromonas gingivalis induces systemic nitric oxide response in mice
A Nemec1, Z Pavlica, D A Crossley
1Veterinary Faculty Small Animal Clinic, University of Ljubljana, Ljubljana, Slovenia. ana.nemec@vf.uni-lj.si
Introduction:
Porphyromonas gingivalis induces nitric oxide (NO) production in various cells, systemic NO elevation being expected in chronic oral challenge.
Methods:
Groups of BALB/c mice were inoculated orally with either live P. gingivalis ATCC 33277 or sterile broth on days 0, 2 and 4, with or without later administration of the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Plasma and tissues were harvested on day 42 for assays of tumor necrosis factor-alpha (TNF-alpha), nitrite and nitrate (NOx) and tissue NO, or histology and iNOS immunohistochemistry.
Results:
No signs of gingivitis were observed, but plasma NOx was significantly elevated (P = 0.028) as was TNF-alpha (P = 0.079) in P. gingivalis-inoculated animals compared with controls, NOx being reduced when 1400W was used. NO production in organs showed a similar trend, with significant elevation in liver (P = 0.017) and kidneys (P = 0.027), whereas concomitant treatment of inoculated animals with 1400W caused significant reductions in NO in aorta (P = 0.008) and kidneys (P = 0.046). Sham-inoculated 1400W-treated animals had significantly increased plasma NOx (P = 0.004) and liver NO (P = 0.04). NOx in plasma correlated significantly with NO production in lungs (0.35, P = 0.032) and kidneys (0.47, P = 0.003). Immunohistochemistry demonstrated iNOS activity in many tissues in all groups.
Conclusion:
Repeated oral administration of P. gingivalis induced systemic NO and NOx production in mice, probably by activating iNOS as suggested by the response to 1400W.
Insights
Porphyromonas gingivalis infection in mice significantly increased nitric oxide (NO) and nitrite/nitrate (NOx) levels, likely by activating inducible nitric oxide synthase (iNOS). Treatment with an iNOS inhibitor reduced these elevated levels.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Porphyromonas gingivalis is known to induce nitric oxide (NO) production.
- Chronic oral infections with P. gingivalis are expected to lead to systemic elevation of NO.
Purpose of the Study:
- To investigate the systemic effects of P. gingivalis oral inoculation on NO production in mice.
- To determine the role of inducible nitric oxide synthase (iNOS) in mediating these effects.
Main Methods:
- Mice were orally inoculated with live P. gingivalis or sterile broth.
- Animals received the iNOS inhibitor 1400W or vehicle.
- Plasma and tissue samples were analyzed for NO, nitrite/nitrate (NOx), and TNF-alpha.
- Immunohistochemistry was used to assess iNOS activity.
Main Results:
- P. gingivalis inoculation led to significantly elevated plasma NOx and TNF-alpha levels.
- Systemic NO production was increased in organs like the liver and kidneys.
- Administration of the iNOS inhibitor 1400W reduced NO and NOx levels.
- iNOS activity was detected in various tissues across all experimental groups.
Conclusions:
- Repeated oral P. gingivalis administration induces systemic NO and NOx production in mice.
- The findings suggest that iNOS activation plays a significant role in this process.
