Cellular dissociation of NF-kappaB and inducible nitric oxide synthase in Helicobacter pylori infection.
The transcription factor nuclear factor kappaB (NF-kappaB) regulates the expression of inducible nitric oxide synthase (iNOS). We hypothesized that induction of iNOS in Helicobacter pylori gastritis may be due to NF-kappaB activation. Antral biopsy specimens from Helicobacter pylori-infected gastritis patients were collected before (n = 30) and after antimicrobial therapy to clear the infection (n = 22). Biopsies were assessed for NF-kappaB by immunohistochemistry (p65). The mRNA and protein of iNOS were localized by in situ RT-PCR and immunohistochemistry. Both of iNOS protein and mRNA were evident in stromal inflammatory cells, but absent in epithelia. Antimicrobial therapy resulted in a 73% reduction in iNOS levels (protein, p <.002). Nuclear staining for NF-kappaB p65 was evident in epithelial cells, especially in the neck region of gastric glands, and inflammatory cells. Treatment to clear H. pylori infection resulted in a 74% reduction in the epithelial staining for NF-kappaB p65 (p =.0001), whereas the lamina propria staining was unaltered. In conclusion, H. pylori infection activates NF-kappaB and iNOS expression. However, as the changes in NF-kappaB and iNOS with H. pylori clearance occurred in different cell types (epithelial vs. inflammatory), it appears that a NF-kappaB-dependent epithelial-derived mediator may be responsible for the induction of iNOS expression.
Zhang
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Department of Pediatrics & Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12054, USA.
Ruiz
B
B
Correa
P
P
Miller
M J
MJ
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004790:Enzyme Induction; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D016328:NF-kappa B; D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II