title: Interleukin-6 induction by Helicobacter pylori in human macrophages is dependent on phagocytosis.
abstract: BACKGROUND
  The colonization of the gastric mucosa with Helicobacter pylori is accompanied by elevated levels of proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and IL-8. The aim of our study was to determine the mechanisms of IL-6 stimulation in phagocytes upon H. pylori infection.
  
  
  METHODS
  We investigated the secretion of IL-6 by different professional phagocytes from murine and human origin, including granulocyte- and monocyte-like cells and macrophages derived from human peripheral blood monocytes (PBMCs). The influence of viability, phagocytosis, and the impact of different subcellular fractions of H. pylori bacteria were evaluated.
  
  
  RESULTS
  IL-6 levels induced by H. pylori were low in cell lines derived from murine and human monocytes and in human granulocyte-like cells. By contrast, macrophages derived from human PBMCs were highly responsive to both H. pylori and Escherichia coli. IL-6 induction was blocked by inhibition of actin-dependent processes prior to infection with H. pylori, but not with E. coli or E. coli lipopolysaccharide (LPS). Using cell fractionation, the most activity was found in the H. pylori membrane. H. pylori LPS exhibited a 10(3)- to 10(4)-fold lower biologic activity than E. coli LPS, suggesting a minor role for toll-like receptor 4 (TLR4)-mediated signalling from the exterior.
  
  
  CONCLUSIONS
  From these data, we conclude that macrophages may be a major source of IL-6 in the gastric mucosa upon H. pylori infection. The IL-6 induction by H. pylori in these cells is a multifactorial process, which requires the uptake and presumably degradation of H. pylori bacteria.
authors: Max von Pettenkofer-Institute for Hygiene und Medical Microbiology, Ludwig-Maximilians-University, Pettenkoferstrasse 9a, D-80336 Munich, Germany. odenbreit@mvp.uni-muenchen.de
authors: Stefan
authors: S
authors: Odenbreit
authors: Stefan
authors: S
authors: Linder
authors: Bettina
authors: B
authors: Gebert-Vogl
authors: Gabriele
authors: G
authors: Rieder
authors: Anthony P
authors: AP
authors: Moran
authors: Rainer
authors: R
authors: Haas