title: Induction of interleukin-8 by Naegleria fowleri lysates requires activation of extracellular signal-regulated kinase in human astroglial cells.
abstract: Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic meningoencephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astroglial cells was investigated following treatment with N. fowleri lysates. We demonstrated that N. fowleri are potent inducers for the expression of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by activation of extracellular signal-regulated kinase (ERK). In addition, N. fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1), an important transcription factor for IL-8 induction. The specific mitogen-activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression requires activation of ERK in human astroglial cells. These findings indicate that treatment of N. fowleri on human astroglial cells leads to the activation of AP-1 and subsequent expression of IL-8 which are dependent on ERK activation. These results may help understand the N. fowleri-mediated upregulation of chemokine and cytokine expression in the astroglial cells.
authors.affiliation: Department of Microbiology, and Molecular Science & Technology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Hae-Jin
authors.initials: HJ
authors.lastname: Sohn
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Daeho
authors.initials: D
authors.lastname: Kwon
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Shin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002070:Butadienes; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016848:Naegleria fowleri / Q000737:chemistry*; D009570:Nitriles; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D002070:Butadienes; D016209:Interleukin-8; D009570:Nitriles; D018808:Transcription Factor AP-1; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases