Cellular dissociation of NF-kappa B and inducible nitric oxide synthase inHelicobacter pylori infection

The transcription factor nuclear factor kappaB (NF-epsilonB) 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 gastr itis patients were collected before (n = 30) and after antimicrobial therap y 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. Antimicrob ial therapy resulted in a 73% reduction in iNOS levels (protein, p < .002). Nuclear staining for NF-<kappa>B p65 was evident in epithelial cells, espe cially in the neck region of gastric glands, and inflammatory cells. Treatm ent to clear H. pylori infection resulted in a 74% reduction in the epithel ial staining far NF-kappaB p65 (p = .0001), whereas the lamina propria stai ning 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. inflammat ory), it appears that a NF-kappaB-dependent epithelial-derived mediator may be responsible for the induction of iNOS expression. (C) 2000 Elsevier Sci ence Inc.