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Helicobacter pylori lipopolysaccharide can activate 70Z/3 cells via CD14
T Kirkland1, S Viriyakosol, G I Perez-Perez
1Department of Pathology, University of California School of Medicine, San Diego 92161, USA.
Abstract:
Helicobacter pylori persistently colonizes the human gastrointestinal tract and is associated with chronic gastritis and, in some cases, peptic ulcer disease or gastric neoplasms. One factor in the persistence of this organism may be its inability to elicit a strong inflammatory response. Lipopolysaccharide (LPS) is a proinflammatory substance found in the cell walls of all gram-negative bacteria. H. pylori LPS has been found by several different measures to be less active than LPS from Enterobacteriaceae. This study addresses the role of CD14 and LPS-binding protein in the cellular response to H. pylori LPS. We report that H. pylori LPS activates mammalian cells expressing CD14 at much lower LPS concentrations than those for control cells not expressing CD14. The maximal activation of CD14-70Z/3 cells by H. pylori LPS also requires LPS-binding protein. H. pylori LPS at concentrations as high as 30 microg/ml does not elicit an interleukin-8 (IL-8) response from the epithelial cell line SW620 in the presence of CD14; 10 ng of Escherichia coli LPS per ml elicits a maximal IL-8 response. Furthermore, in contrast to some other types of LPS with little activity, H. pylori LPS does not inhibit the CD14-70Z/3 cell response to E. coli LPS. From these studies, we conclude that H. pylori LPS, though much less active than E. coli LPS, stimulates cells via CD14.
Insights
Helicobacter pylori lipopolysaccharide (LPS) activates CD14-expressing cells at low concentrations, requiring LPS-binding protein for maximal response. This indicates H. pylori LPS stimulates cells via CD14 despite lower activity than E. coli LPS.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Helicobacter pylori is a persistent gastrointestinal pathogen linked to gastritis and gastric cancers.
- Bacterial lipopolysaccharide (LPS) typically triggers inflammation, but H. pylori LPS shows reduced activity compared to other Gram-negative bacteria.
- The cellular mechanisms underlying H. pylori LPS hyporesponsiveness are not fully understood.
Purpose of the Study:
- To investigate the role of CD14 and LPS-binding protein (LBP) in cellular responses to H. pylori LPS.
- To compare the activation potential of H. pylori LPS with Escherichia coli LPS in CD14-dependent pathways.
Main Methods:
- Utilized cell lines expressing CD14 (CD14-70Z/3) and epithelial cells (SW620).
- Assessed cellular activation, specifically interleukin-8 (IL-8) production, in response to varying concentrations of H. pylori LPS and E. coli LPS.
- Investigated the requirement of LPS-binding protein (LBP) for H. pylori LPS-mediated cell activation.
Main Results:
- H. pylori LPS activated CD14-expressing cells at significantly lower concentrations than control cells.
- Maximal activation by H. pylori LPS in CD14-70Z/3 cells necessitated the presence of LPS-binding protein.
- H. pylori LPS did not induce an IL-8 response in SW620 cells even at high concentrations, unlike E. coli LPS.
- H. pylori LPS did not inhibit the response of CD14-70Z/3 cells to E. coli LPS.
Conclusions:
- H. pylori LPS, despite its low inflammatory potential, can stimulate mammalian cells through the CD14 pathway.
- LPS-binding protein is crucial for mediating the cellular response to H. pylori LPS.
- The findings elucidate a mechanism for H. pylori's persistence by modulating host inflammatory responses via CD14.