title: Induction of proinflammatory mediators requires activation of the TRAF, NIK, IKK and NF-kappaB signal transduction pathway in astrocytes infected with Escherichia coli.
abstract: Escherichia coli is associated with inflammation in the brain. To investigate whether astrocytes are involved in E. coil-induced inflammation, we assessed the levels of expression of proinflammatory mediators produced by E. coli-infected astrocytes. E. coli infection in primary human astrocytes and cell lines increased expression of the CXC chemokine IL-8/GRO-alpha, the CC chemokine MCP-1, TNF-alpha, and iNOS. E. coli infection activated p65/p50 heterodimeric NF-kappaB and concurrently decreased the signals of IkappaBalpha. Blocking the NF-kappaB signals by IkappaBalpha-superrepressor-containing retrovirus or antisense p50 oligonucleotide transfection resulted in down-regulation of expression of the proinflammatory mediators. Furthermore, superrepressors of IkappaBalpha, IkappaB kinase (IKK) or NF-kappaB inducing kinase (NIK) inhibited the up-regulated expression of the downstream target genes of NF-kappaB such as IL-8 and MCP-1, and superrepressors of TNF receptor-associated factor (TRAF)2 and TRAF5 also inhibited expression of the E. coli-induced target genes of NF-kappaB. These results indicate that proinflammatory mediators such as the CXC chemokine IL-8/GRO-alpha, the CC chemokine MCP-1, TNF-alpha, and iNOS can be expressed in E. coli-infected astrocytes via an NF-kappaB pathway, suggesting that these mediators may contribute to inflammation in the brain, including infiltration of inflammatory cells.
authors.affiliation: Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea. jungmogg@hanyang.ac.kr
authors.forename: J M
authors.initials: JM
authors.lastname: Kim
authors.forename: Y-K
authors.initials: YK
authors.lastname: Oh
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: D Y
authors.initials: DY
authors.lastname: Im
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Youn
authors.forename: C-H
authors.initials: CH
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Son
authors.forename: Y-S
authors.initials: YS
authors.lastname: Lee
authors.forename: J Y
authors.initials: JY
authors.lastname: Park
authors.forename: I-H
authors.initials: IH
authors.lastname: Choi
mesh_terms: D001253:Astrocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000276:immunology; D054360:Chemokine CXCL1; D018925:Chemokines / Q000276:immunology*; D019743:Chemokines, CXC / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology*; D006801:Humans; D051550:I-kappa B Kinase; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000276:immunology*; D047992:TNF Receptor-Associated Factor 2 / Q000276:immunology; D048015:TNF Receptor-Associated Factor 5 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; C475829:CXCL1 protein, human; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D047992:TNF Receptor-Associated Factor 2; D048015:TNF Receptor-Associated Factor 5; D014409:Tumor Necrosis Factor-alpha; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human