Merck
  • Home
  • Search Results
  • Heme oxygenase-1 dysregulates macrophage polarization and the immune response to Helicobacter pylori.

Heme oxygenase-1 dysregulates macrophage polarization and the immune response to Helicobacter pylori.

Journal of immunology (Baltimore, Md. : 1950) (2014-08-12)
Alain P Gobert, Thomas Verriere, Mohammad Asim, Daniel P Barry, M Blanca Piazuelo, Thibaut de Sablet, Alberto G Delgado, Luis E Bravo, Pelayo Correa, Richard M Peek, Rupesh Chaturvedi, Keith T Wilson
ABSTRACT

Helicobacter pylori incites a futile inflammatory response, which is the key feature of its immunopathogenesis. This leads to the ability of this bacterial pathogen to survive in the stomach and cause peptic ulcers and gastric cancer. Myeloid cells recruited to the gastric mucosa during H. pylori infection have been directly implicated in the modulation of host defense against the bacterium and gastric inflammation. Heme oxygenase-1 (HO-1) is an inducible enzyme that exhibits anti-inflammatory functions. Our aim was to analyze the induction and role of HO-1 in macrophages during H. pylori infection. We now show that phosphorylation of the H. pylori virulence factor cytotoxin-associated gene A (CagA) in macrophages results in expression of hmox-1, the gene encoding HO-1, through p38/NF (erythroid-derived 2)-like 2 signaling. Blocking phagocytosis prevented CagA phosphorylation and HO-1 induction. The expression of HO-1 was also increased in gastric mononuclear cells of human patients and macrophages of mice infected with cagA(+) H. pylori strains. Genetic ablation of hmox-1 in H. pylori-infected mice increased histologic gastritis, which was associated with enhanced M1/Th1/Th17 responses, decreased regulatory macrophage (Mreg) response, and reduced H. pylori colonization. Gastric macrophages of H. pylori-infected mice and macrophages infected in vitro with this bacterium showed an M1/Mreg mixed polarization type; deletion of hmox-1 or inhibition of HO-1 in macrophages caused an increased M1 and a decrease of Mreg phenotype. These data highlight a mechanism by which H. pylori impairs the immune response and favors its own survival via activation of macrophage HO-1.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
LY-294,002 hydrochloride, solid, ≥98% (HPLC)
Sigma-Aldrich
Bay 11-7082, ≥98% (HPLC), powder
Sigma-Aldrich
SP600125, ≥98% (HPLC)
Sigma-Aldrich
Chromium, powder, ≥99% trace metals basis, <45 μm
Sigma-Aldrich
Chromium, powder, 99.5%, −100 mesh
Sigma-Aldrich
Chromium, chips, thickness ~2 mm, 99.5%
Sigma-Aldrich
Chromium, chips, 99.995% trace metals basis
Sigma-Aldrich
Cytochalasin D, Ready Made Solution, from Zygosporium mansonii, 5 mg/mL in DMSO
Sigma-Aldrich
Cytochalasin D, from Zygosporium mansonii, ≥98% (TLC and HPLC), powder
Chromium, rod, 10mm, diameter 5.0mm, 99.7+%
Chromium, foil, light tested, 25x25mm, thickness 0.075mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 50x50mm, thickness 0.015mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.0125mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.0125mm, permanent polyester support, 99.99+%
Chromium, foil, light tested, 25x25mm, thickness 0.05mm, permanent polyester support, 99.99+%
Chromium, microfoil, disks, 10mm, thinness 0.25μm, specific density 178.7μg/cm2, permanent mylar 3.5μm support, 99.99+%
Chromium, foil, not light tested, 50x50mm, thickness 0.002mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.001mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.015mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.015mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 25x25mm, thickness 0.009mm, permanent polyester support, 99.99+%
Chromium, microfoil, disks, 10mm, thinness 0.5μm, specific density 355μg/cm2, permanent mylar 3.5μm support, 99.99+%
Chromium, foil, not light tested, 50x50mm, thickness 0.003mm, permanent polyester support, 99.99+%
Chromium, microfoil, disks, 25mm, thinness 1.0μm, specific density 719μg/cm2, permanent mylar 3.5μm support, 99.99+%
Chromium, foil, not light tested, 50x50mm, thickness 0.008mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 50x50mm, thickness 0.025mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 100x100mm, thickness 0.01mm, permanent polyester support, 99.99+%
Chromium, foil, not light tested, 50x50mm, thickness 0.004mm, permanent polyester support, 99.99+%
Chromium, rod, 100mm, diameter 2.0mm, 99.7+%
Chromium, foil, not light tested, 50x50mm, thickness 0.01mm, permanent polyester support, 99.99+%