title: Porphyromonas gingivalis culture supernatants differentially regulate interleukin-1beta and interleukin-18 in human monocytic cells.
abstract: Porphyromonas gingivalis is a major bacterial species implicated in chornic periodontitis, a disease characterized by inflammatory destruction of the tooth supporting tissues. Its main virulence factors are lipopolysaccharide (LPS) and gingipains, a group of cysteine proteinases. Interleukin (IL)-18 is a potent pro-inflammatory cytokine with structural similarities to IL-1beta. This study aimed to investigate if P .gingivalis regulates IL-1beta and IL-18 in monocytic cells. Monomac-6 cells were challenged with P. gingivalis culture supernatants. Quantitative real-time PCR and ELISA were used to investigate IL-1beta and IL-18 mRNA expression and protein secretion, respectively. P. gingivalis enhanced IL-1beta and IL-18 mRNA expression, the former being induced earlier, but transiently. IL-18 up-regulation was not affected by P. gingivalis heat-inactivation or chemical inhibition of its gingipains, whereas both treatments resulted in 50% reduction of IL-1beta expression. Purified P. gingivalis LPS enhanced both IL-1beta and IL-18 expression. However, only IL-1beta, but not IL-18, secretion was detected, and was up-regulated by P. gingivalis. In conclusion, although IL-1beta and IL-18 belong to the same cytokine family, their gene expression and secretion are differentially regulated in human monocytic cells in response to P. gingivalis. Therefore, cytokines of the IL-1 family may participate via different pathways in the complex pathogenesis of periodontitis.
authors.affiliation: Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hamedi
authors.forename: G N
authors.initials: GN
authors.lastname: Belibasakis
authors.forename: A T
authors.initials: AT
authors.lastname: Cruchley
authors.forename: M
authors.initials: M
authors.lastname: Rangarajan
authors.forename: M A
authors.initials: MA
authors.lastname: Curtis
authors.forename: N
authors.initials: N
authors.lastname: Bostanci
mesh_terms: D000818:Animals; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry*; D005881:Gingiva / Q000276:immunology / Q000382:microbiology; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D003470:Culture Media; D020382:Interleukin-18; D053583:Interleukin-1beta