Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production.
OBJECTIVE
Helicobacter pylori surface proteins induce the production of proinflammatory mediators by mononuclear phagocytes, but the protein responsible for this stimulation has not been identified. This study determined whether urease, the major component of the soluble proteins extracted from H. pylori grown in culture, activates mononuclear phagocytes and stimulates them to produce proinflammatory cytokines.


METHODS
Primary human blood monocytes were incubated with column-purified H. pylori urease and assayed by flow cytometry, Immunoassay, and reverse-transcription polymerase chain reaction for phenotypic, functional, and molecular evidence of activation.


RESULTS
H. pylori urease induced monocyte expression of surface interleukin 2 receptors and increased expression of HLA-DR, phenotypic changes consistent with activation. Urease also stimulated dose-dependent production of interleukin 1 beta, interleukin 6, interleukin 8, and tumor necrosis factor alpha peptides and messenger RNA. These urease-induced phenotypic and functional changes were inhibited by preincubation of the urease with antisera to H. pylori whole bacteria, purified urease, or the 31-kilodalton subunit of urease.


CONCLUSIONS
Among the soluble proteins released by H. pylori, urease is capable of activating monocytes for proinflammatory cytokines production. The local production of cytokines by urease-stimulated mononuclear phagocytes may play a central role in the development of H. pylori gastroduodenal inflammation.
Harris
P R
PR
Department of Pediatrics, University of Alabama School of Medicine, Birmingham, USA.
Mobley
H L
HL
Perez-Perez
G I
GI
Blaser
M J
MJ
Smith
P D
PD
D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006684:HLA-DR Antigens / Q000378:metabolism; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014510:Urease / Q000494:pharmacology*
D016207:Cytokines; D006684:HLA-DR Antigens; D007378:Interleukins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D014510:Urease