title: Porphyromonas gingivalis RagB is a proinflammatory signal transducer and activator of transcription 4 agonist.
abstract: Periodontal diseases are semi-ubiquitous and caused by chronic, plaque-induced inflammation. The 55-kDa immunodominant RagB outer membrane protein of Porphyromonas gingivalis, a keystone periodontal pathogen, has been proposed to facilitate nutrient transport. However, potential interactions between RagB and the innate response have not been examined. We determined that RagB exposure led to the differential and dose-related expression of multiple genes encoding proinflammatory mediators [interleukin-1α (IL-1α), IL-1β, IL-6, IL-8 and CCL2; all P < 0.05] in primary human monocytes and to the secretion of tumor necrosis factor and IL-8, but not interferon-γ or IL-12. RagB was shown to be a Toll-like receptor 2 (TLR2) and TLR4 agonist that activated signal transducer and activator of transcription 4 and nuclear factor-κB signaling, as determined by a combination of blocking antibodies, pharmaceutical inhibitors and gene silencing. In keeping, a ΔragB mutant similarly exhibited reduced inflammatory capacity, which was rescued by ragB complementation. These results suggest that RagB elicits a major pro-inflammatory response in primary human monocytes and, therefore, could play an important role in the etiology of periodontitis and systemic sequelae.
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Hutcherson
authors.forename: J
authors.initials: J
authors.lastname: Bagaitkar
authors.forename: K
authors.initials: K
authors.lastname: Nagano
authors.forename: F
authors.initials: F
authors.lastname: Yoshimura
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: D A
authors.initials: DA
authors.lastname: Scott
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005881:Gingiva / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D010518:Periodontitis / Q000276:immunology; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000235:genetics*; D050797:STAT4 Transcription Factor / Q000819:agonists*; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D051197:Toll-Like Receptor 4 / Q000819:agonists*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C484346:RagB protein, bacteria; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Porphyromonas gingivalis; Toll-like receptor; inflammation; monocyte; periodontitis; signal transducer and activator of transcription 4