Up-regulation of inducible nitric oxide synthase and nitric oxide in Helicobacter pylori-infected human gastric epithelial cells: possible role of interferon-gamma in polarized nitric oxide secretion

Kim, JM; Kim, JS; Jung, HC; Song, IS; Kim, CY

HERO ID

1656140

Reference Type

Journal Article

Year

2002

Language

English

PMID

11966872

HERO ID 1656140
In Press No
Year 2002
Title Up-regulation of inducible nitric oxide synthase and nitric oxide in Helicobacter pylori-infected human gastric epithelial cells: possible role of interferon-gamma in polarized nitric oxide secretion
Authors Kim, JM; Kim, JS; Jung, HC; Song, IS; Kim, CY
Journal Helicobacter
Volume 7
Issue 2
Page Numbers 116-128
Abstract <strong>BACKGROUND: </strong>Nitric oxide (NO) generated by nitric oxide synthase (NOS) is known to be an important modulator of the mucosal inflammatory response. In this study, we questioned whether Helicobacter pylori infection could up-regulate the epithelial cell inducible NOS (iNOS) gene expression and whether NO production could show polarity that can be regulated by immune mediators.<br /><br /><strong>MATERIALS AND METHODS: </strong>Human gastric epithelial cell lines were infected with H. pylori, and the iNOS mRNA expression was assessed by quantitative RT-PCR. NO production was assayed by determining nitrite/nitrate levels in culture supernatants. To determine the polarity of NO secretion by the H. pylori-infected epithelial cells, Caco-2 cells were cultured as polarized monolayers in transwell chambers, and NO production was measured.<br /><br /><strong>RESULTS: </strong>iNOS mRNA levels were significantly up-regulated in the cells infected with H. pylori, and expression of iNOS protein was confirmed by Western blot analysis. Increased NO production in the gastric epithelial cells was seen as early as 18 hours postinfection, and reached maximal levels by 24 hours postinfection. The specific MAP kinase inhibitors decreased H. pylori-induced iNOS and NO up-regulation. After H. pylori infection of polarized epithelial cells, NO was released predominantly into the apical compartment, and IL-8 was released predominantly into basolateral compartment. The addition of IFN-gamma to H. pylori-infected polarized epithelial cells showed a synergistically higher apical and basolateral NO release.<br /><br /><strong>CONCLUSION: </strong>These results suggest that apical NO production mediated by MAP kinase in H. pylori-infected gastric epithelial cells may influence the bacteria and basolateral production of NO and IL-8 may play a role in the tissue inflammation.
Doi 10.1046/j.1083-4389.2002.00068.x
Pmid 11966872
Wosid WOS:000175126600009
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword epithelial cells; Helicobacter pylori; inducible nitric oxide; interferon-gamma; polarity