title: TGF-beta1 Inhibits TLR-mediated odontoblast responses to oral bacteria.
abstract: TGF-beta1 exerts diverse functions in tooth development and tissue repair, but its role in microbial defenses of the tooth is not well-understood. Odontoblasts extending their cellular processes into the dentin are the first cells to recognize signals from TGF-beta1 and bacteria in carious dentin. This study aimed to determine the role of TGF-beta1 in modulating odontoblast responses to oral bacteria. We show that these responses depend upon the expression levels of microbial recognition receptors TLR2 and TLR4 on the cell surface. Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum activated both TLRs, but TLR4 played a greater role. Lack of cell-surface TLR2 was associated with poor response to Streptococcus mutans, Enterococcus faecalis, and Lactobacillus casei. TGF-beta1 inhibited TLR2 and TLR4 expression and attenuated odontoblast responses. Our findings suggest that the balance between TLR-mediated inflammation and TGF-beta1 anti-inflammatory activity plays an important role in pulpal inflammation.
authors.affiliation: Department of Oral Biology, University of Washington, Seattle, WA 98195-7132, USA.
authors.forename: O V
authors.initials: OV
authors.lastname: Horst
authors.forename: K A
authors.initials: KA
authors.lastname: Tompkins
authors.forename: S R
authors.initials: SR
authors.lastname: Coats
authors.forename: P H
authors.initials: PH
authors.lastname: Braham
authors.forename: R P
authors.initials: RP
authors.lastname: Darveau
authors.forename: B A
authors.initials: BA
authors.lastname: Dale
mesh_terms: D002999:Clone Cells; D003731:Dental Caries / Q000209:etiology / Q000276:immunology* / Q000382:microbiology; D016905:Gram-Negative Bacterial Infections / Q000150:complications / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000150:complications / Q000276:immunology; D006801:Humans; D009804:Odontoblasts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011671:Pulpitis / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000502:physiology; D012044:Regression Analysis; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1