Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line.
OBJECTIVE
Helicobacter pylori uniquely colonizes the human stomach and produces gastric mucosal inflammation. High-output nitric oxide production by inducible nitric oxide synthase (iNOS) is associated with immune activation and tissue injury. Because mononuclear cells comprise a major part of the cellular inflammatory response to H. pylori infection, the ability of H. pylori to induce iNOS in macrophages was assessed.


METHODS
H. pylori preparations were added to RAW 264.7 murine macrophages, and iNOS expression was assessed by Northern blot analysis, enzyme activity assay, and NO2- release.


RESULTS
Both whole H. pylori and French press lysates induced concentration-dependent NO2- production, with peak levels 20-fold above control. These findings were paralleled by marked increases in iNOS messenger RNA and enzyme activity levels. iNOS expression was synergistically increased with interferon gamma, indicating that the H. pylori effect can be amplified by other macrophage-activating factors. Studies of lipopolysaccharide (LPS) content and polymyxin B inhibition of LPS suggested that the H. pylori effect was attributable to both LPS-dependent and -independent mechanisms.


CONCLUSIONS
iNOS expression in macrophages is activated by highly stable H. pylori products and may play an important role in the pathogenesis of H. pylori-associated gastric mucosal disease.
Wilson
K T
KT
Department of Medicine, University of Maryland School of Medicine, Baltimore, USA. kwilson@umabnet.ab.umd.edu
Ramanujam
K S
KS
Mobley
H L
HL
Musselman
R F
RF
James
S P
SP
Meltzer
S J
SJ
D000818:Animals; D002460:Cell Line; D016481:Helicobacter Infections / Q000201:enzymology*; D016480:Helicobacter pylori; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology / Q000382:microbiology*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*
D007371:Interferon-gamma; D019001:Nitric Oxide Synthase