title: Interleukin-1beta modulates proinflammatory cytokine production in human epithelial cells.
abstract: Periodontitis is a chronic human inflammatory disease initiated and sustained by dental plaque microorganisms. A major contributing pathogen is Porphyromonas gingivalis, a gram-negative bacterium recognized by Toll-like receptor 2 (TLR2) and TLR4, which are expressed by human gingival epithelial cells (HGECs). However, it is still unclear how these cells respond to P. gingivalis and initiate inflammatory and immune responses. We have reported previously that HGECs produce a wide range of proinflammatory cytokines, including interleukin-6 (IL-6), IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha (TNF-alpha), and IL-1beta. In this study, we show that IL-1beta has a special role in the modulation of other inflammatory cytokines in HGECs challenged with P. gingivalis. Our results show that the increased production of IL-1beta correlates with the cell surface expression of TLR4, and more specifically, TLR4-normal HGECs produce fourfold more IL-1beta than do TLR4-deficient HGECs after challenge. Moreover, blocking the IL-1beta receptor greatly reduces the production of "secondary" proinflammatory cytokines such as IL-8 or IL-6. Our data indicate that the induction of IL-1beta plays an important role in mediating the release of other proinflammatory cytokines from primary human epithelial cells following challenge with P. gingivalis, and this process may be an inflammatory enhancement mechanism adopted by epithelial cells.
authors.affiliation: University of Louisville School of Dentistry, Louisville, KY 40292, USA.
authors.forename: Mehmet A
authors.initials: MA
authors.lastname: Eskan
authors.forename: Manjunatha R
authors.initials: MR
authors.lastname: Benakanakere
authors.forename: Beate G
authors.initials: BG
authors.lastname: Rose
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Jiawei
authors.initials: J
authors.lastname: Zhao
authors.forename: Panagiota
authors.initials: P
authors.lastname: Stathopoulou
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Denis F
authors.initials: DF
authors.lastname: Kinane
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000276:immunology*; D020868:Gene Silencing; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4