title: Effect of exogenous nitric oxide on murine immune response induced by Aggregatibacter actinomycetemcomitans lipopolysaccharide.
abstract: OBJECTIVE
  Elevated nitric oxide (NO) has been associated with destructive periodontal disease. The aim of the present study was to test the hypothesis that exogenous NO may inhibit a protective immune response to Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) in a murine model.
  
  
  METHODS
  Mice of the BALB/c strain were sham immunized, immunized with A. actinomycetemcomitans LPS, treated with S-nitroso-N-acetyl penicillamine (SNAP; a NO donor) and immunized with A. actinomycetemcomitans LPS or treated with SNAP plus 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and immunized with A. actinomycetemcomitans LPS. All animals were then challenged subcutaneously with viable A. actinomycetemcomitans. The serum-specific immunoglobulin G (IgG) subclasses and both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) as well as splenic inducible nitric oxide synthase (iNOS) activity before and after bacterial challenge were assessed. The diameter of skin lesions was determined. Groups of mice were treated with l-N(6)-(1-iminoethyl)-lysine (l-NIL), an iNOS inhibitor, or 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), a guanylyl cyclase inhibitor, prior to injections with SNAP and/or A. actinomycetemcomitans LPS, and the skin lesions were assessed.
  
  
  RESULTS
  Treatment with SNAP increased the iNOS activity, suppressed both serum-specific IgG2a and IFN-gamma levels, and delayed the healing of the lesions. These SNAP-induced immune alterations were restored by treatment with carboxy-PTIO. Pretreatment with l-NIL resulted in partial healing, whereas pretreatment with ODQ induced a delayed healing of the lesions.
  
  
  CONCLUSIONS
  The present study suggests that exogenous NO may suppress a protective T helper 1-like murine immune response to A. actinomycetemcomitans LPS by an endogenous NO-independent but a cyclic GMP-dependent mechanism.
authors.affiliation: School of Dentistry, AIMST University, Semeling, Bedong, Kedah, Darul Aman, Malaysia. wsosroseno@yahoo.com
authors.forename: W
authors.initials: W
authors.lastname: Sosroseno
authors.forename: P S
authors.initials: PS
authors.lastname: Bird
authors.forename: G J
authors.initials: GJ
authors.lastname: Seymour
mesh_terms: D000189:Actinobacillus Infections / Q000276:immunology; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001565:Benzoates / Q000494:pharmacology; D006152:Cyclic GMP / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000494:pharmacology; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D017192:Skin Diseases, Bacterial / Q000276:immunology; D013154:Spleen / Q000201:enzymology; D018417:Th1 Cells / Q000276:immunology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000907:Antibodies, Bacterial; D001565:Benzoates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C090663:N(6)-(1-iminoethyl)lysine; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D015847:Interleukin-4; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008239:Lysine