title: Synergistic induction of inflammation by bacterial products lipopolysaccharide and fMLP: an important microbial pathogenic mechanism.
abstract: A wide variety of stimuli have been shown to induce inflammation, but bacteria products/components are considered the major inducers during bacterial infections. We previously demonstrated that bacterial products/components such as LPS, a glycolipid component of the bacterial outer membrane, and formylated peptides (fMLP), a bacterial-derived peptide, induced proinflammatory cytokine gene expression in human peripheral blood monocytes. We now present evidence that mixtures of bacterial products/components LPS and fMLP behave synergistically in the induction of inflammation in vitro and in vivo. Furthermore, our results indicate that the TLR4 and the IKKbeta-IkappaBalpha signaling pathways are involved in the synergistic induction of inflammatory cytokines. The mechanism of synergistic activation of NF-kappaB is depended on nuclear translocation of p65 and phosphorylation of p65 at both Ser536 and Ser276 sites. These results demonstrate an important role for bacterial products/components from lysed bacteria in the pathogenesis of infectious diseases. We believe that this synergistic induction of inflammation by bacterial products LPS and fMLP represents an important pathogenic mechanism during bacterial infection, which may suggest novel therapeutic strategies or targets to minimize host injury following bacterial infection.
authors.affiliation: Department of Medical Microbiology and Immunology, Medical University of Ohio, Toledo, OH 43614, USA.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Chen
authors.forename: Warren W
authors.initials: WW
authors.lastname: Pan
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.forename: Jain-Dong
authors.initials: JD
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chen
authors.forename: Shuang
authors.initials: S
authors.lastname: Huang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Papadimos
authors.forename: Zhixing K
authors.initials: ZK
authors.lastname: Pan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D044042:Receptors, Formyl Peptide / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D044042:Receptors, Formyl Peptide; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha