title: Suppression of cell division-associated genes by Helicobacter pylori attenuates proliferation of RAW264.7 monocytic macrophage cells.
abstract: Helicobacter pylori at multiplicity of infection (MOI ≥ 50) have been shown to cause apoptosis in RAW264.7 monocytic macrophage cells. Because chronic gastric infection by H. pylori results in the persistence of macrophages in the host's gut, it is likely that H. pylori is present at low to moderate, rather than high numbers in the infected host. At present, the effect of low-MOI H. pylori infection on macrophage has not been fully elucidated. In this study, we investigated the genome-wide transcriptional regulation of H. pylori-infected RAW264.7 cells at MOI 1, 5 and 10 in the absence of cellular apoptosis. Microarray data revealed up- and down-regulation of 1341 and 1591 genes, respectively. The expression of genes encoding for DNA replication and cell cycle-associated molecules, including Aurora-B kinase (AurkB) were down-regulated. Immunoblot analysis verified the decreased expression of AurkB and downstream phosphorylation of Cdk1 caused by H. pylori infection. Consistently, we observed that H. pylori infection inhibited cell proliferation and progression through the G1/S and G2/M checkpoints. In summary, we suggest that H. pylori disrupts expression of cell cycle-associated genes, thereby impeding proliferation of RAW264.7 cells, and such disruption may be an immunoevasive strategy utilized by H. pylori.
authors.affiliation: Department of Medical Microbiology.
authors.forename: Grace Min Yi
authors.initials: GM
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.affiliation: Department of Medical Microbiology.
authors.forename: Keith Conrad
authors.initials: KC
authors.lastname: Fernandez
authors.affiliation: Department of Medical Microbiology.
authors.forename: Jamuna
authors.initials: J
authors.lastname: Vadivelu
authors.affiliation: Department of Medical Microbiology.
authors.forename: Mun Fai
authors.initials: MF
authors.lastname: Loke
authors.affiliation: 1] Department of Medical Microbiology [2] Tropical Infectious Disease Research and Education Center, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Won Fen
authors.initials: WF
authors.lastname: Wong
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000235:genetics / Q000276:immunology; D058491:Bacterial Load; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000235:genetics* / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D004261:DNA Replication / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D057131:Immune Evasion; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation
chemical_list: D018797:Cell Cycle Proteins; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D016203:CDC2 Protein Kinase