title: RahU: an inducible and functionally pleiotropic protein in Pseudomonas aeruginosa modulates innate immunity and inflammation in host cells.
abstract: The aim of this study was to define the functional role of a recently identified RahU protein from Pseudomonas aeruginosa in macrophages and its role in bacterial defense. Recombinant (r)-RahU had no significant effect on cell apoptosis or cell viability in human monocytic THP-1 cells. Gene expression array of murine macrophage cells (RAW 264.7) stimulated with LPS showed modulation of common transcripts (by r-RahU and predisone) involved in inflammation. Functional cellular analysis showed RAW cells incubated with r-RahU at 1.0-10 μg/ml (0.06-0.6 μM) inhibited accumulation of nitric oxide (NO) in the presence of LPS by 10-50%. The IC(50) of r-RahU (0.6 μM) was distinct from the known inhibitors of NO production: prednisone (50 μM) and L-NMMA (100 μM). r-RahU also significantly inhibited chemotactic activity of THP-1 cells toward CCL2 or chemotactic supernatants from apoptotic T-cells. These reports show previously unknown pleiotropic properties of RahU in modulating both microbial physiology and host innate immunity.
authors.affiliation: Research Department, Carilion Clinic and Virginia Tech, Carilion School of Medicine, Roanoke, VA 24013, USA.
authors.forename: Jayasimha
authors.initials: J
authors.lastname: Rao
authors.forename: Michael R
authors.initials: MR
authors.lastname: Elliott
authors.forename: Norbert
authors.initials: N
authors.lastname: Leitinger
authors.forename: Roderick V
authors.initials: RV
authors.lastname: Jensen
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Amin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D054884:Host-Pathogen Interactions / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000209:etiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D011994:Recombinant Proteins; D009569:Nitric Oxide