title: Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways.
abstract: Streptococcus intermedius is a commensal associated with serious, deep-seated purulent infections in major organs, such as the brain and liver. Histone-like DNA binding protein (HLP) is an accessory architectural protein in a variety of bacterial cellular processes. In this study, we investigated the mechanisms of pro-inflammatory cytokine inductions in THP-1 cells by stimulation with recombinant HLP of S. intermedius (rSi-HLP). rSi-HLP stimulation-induced production of pro-inflammatory cytokines (IL-8, IL-1 beta and TNF-alpha) occurred in a time- and dose-dependent manner. In contrast with the heat-stable activity of DNA binding, the induction activity of rSi-HLP was heat-unstable. In subsequent studies, rSi-HLP acted cooperatively with lipoteichoic acid, the synthetic Toll-like receptor 2 agonist, Pam3CSK4, and the cytosolic nucleotide binding oligomerization domain 2 receptor agonist, muramyldipeptide. Furthermore, Western blot and blocking assays with specific inhibitors showed that rSi-HLP stimulation induced the activation of cell signal transduction pathways, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). In addition to its physiological role in bacterial growth through DNA binding, these results indicate that Si-HLP can trigger a cascade of events that induce pro-inflammatory responses via ERK1/2 and JNK signal pathways, and suggest that bacterial HLP may contribute to the activation of host innate immunity during bacterial infection.
authors: Department of Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8504, Japan.
authors: Dali
authors: D
authors: Liu
authors: Hiromichi
authors: H
authors: Yumoto
authors: Katsuhiko
authors: K
authors: Hirota
authors: Keiji
authors: K
authors: Murakami
authors: Kanako
authors: K
authors: Takahashi
authors: Kouji
authors: K
authors: Hirao
authors: Takashi
authors: T
authors: Matsuo
authors: Kazuto
authors: K
authors: Ohkura
authors: Hideaki
authors: H
authors: Nagamune
authors: Yoichiro
authors: Y
authors: Miyake
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000382:microbiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D034367:Streptococcus intermedius / Q000235:genetics / Q000276:immunology*; D013682:Teichoic Acids / Q000276:immunology; D015854:Up-Regulation
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013682:Teichoic Acids; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C009900:lipoteichoic acid; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3