title: Autoregulatory effect of interleukin-10 on proinflammatory cytokine production by Porphyromonas gingivalis lipopolysaccharide-tolerant human monocytes.
abstract: Pretreatment of human peripheral blood monocytes with a very low concentration (0.1 ng/ml) of Porphyromonas gingivalis lipopolysaccharides (LPS) resulted in a significant decrease of interleukin-6 (IL-6) production, but not IL-8 production, by restimulation of a high concentration (1 microg/ml) of the same LPS. In contrast, the same pretreatment with Escherichia coli LPS resulted in the enhanced production of both IL-6 and IL-8 after restimulation. The selective induction by P. gingivalis LPS tolerance of IL-6 production developed in a time-dependent manner during the primary culture. P. gingivalis LPS-pretreated cells were also refractory to a high-dose E. coli LPS restimulation in terms of IL-6 production. The expression of IL-6 mRNA decreased 10 h after restimulation of P. gingivalis LPS-pretreated monocytes. Furthermore, an up-regulation of anti-inflammatory cytokine IL-10 upon a second high-dose LPS rechallenge occurred at the same time point in the pretreated cells. We studied the role of IL-10 in the process of IL-6 down-regulation. Neutralization by an anti-IL-10 polyclonal antibody prevented IL-6 down-regulation in P. gingivalis LPS-pretreated monocytes, whereas IL-8 production was not affected. Addition of exogenous IL-10 during the high-dose LPS stimulation of untreated cells substituted for the LPS pretreatment and resulted in the inhibition of IL-6 production in a dose-dependent manner. A higher dose of IL-10 was required to suppress IL-8 synthesis from monocytes. Our data suggest that IL-10 mediates IL-6 down-regulation in P. gingivalis LPS-tolerant monocytes in an autocrine manner.
authors.affiliation: Department of Periodontology and Endodontology, Osaka University Faculty of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan. simauti@dent.osaka-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Shimauchi
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
authors.forename: K
authors.initials: K
authors.lastname: Okuda
authors.forename: Y
authors.initials: Y
authors.lastname: Kusumoto
authors.forename: H
authors.initials: H
authors.lastname: Okada
mesh_terms: D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D009500:Neutralization Tests; D016966:Porphyromonas gingivalis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10