title: IL-1β and IL-6 activate inflammatory responses of astrocytes against Naegleria fowleri infection via the modulation of MAPKs and AP-1.
abstract: Naegleria fowleri, a free-living amoeba, has been found in diverse habitats throughout the world. It causes primary amoebic meningoencephalitis in children and young adults. The amoeba attaches to nasal mucosa, migrates along olfactory nerves and enters the brain. Astrocytes are involved in the defence against infection and produce inflammatory responses. In this study, we focus on the mechanism of immune responses in astrocytes. We showed, using RNase protection assay, RT-PCR and ELISA in an in vitro culture system, that N. fowleri lysates induce interleukin-1beta (IL-1β) and IL-6 expression of astrocytes. In addition, cytokine levels of astrocytes gradually decreased due to extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 inhibitors. To determine the transcription factor, we used transcription inhibitor (AP-1 inhibitor), which downregulated IL-1β and IL-6 expression. These results show that AP-1 is related to IL-1β and IL-6 production. N. fowleri-mediated IL-1β and IL-6 expression requires ERK, JNK and p38 mitogen-activated protein kinases (MAPKs) activation in astrocytes. These findings show that N. fowleri-stimulated astrocytes in an in vitro culture system lead to AP-1 activation and the subsequent expressions of IL-1β and IL-6, which are dependent on ERK, JNK and p38 MAPKs activation. These results may imply that proinflammatory cytokines have important roles in inflammatory responses to N. fowleri infection.
authors.affiliation: Department of Microbiology, Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: A-R
authors.initials: AR
authors.lastname: Song
authors.affiliation: Department of Microbiology, Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Sohn
authors.affiliation: Department of Microbiology, Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: J-K
authors.initials: JK
authors.lastname: Yoo
authors.affiliation: Department of Microbiology, School of Medicine, Kwandong University, Gangneung, Republic of Korea.
authors.forename: D
authors.initials: D
authors.lastname: Kwon
authors.affiliation: Department of Microbiology, Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Shin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000276:immunology* / Q000469:parasitology*; D002478:Cells, Cultured; D053583:Interleukin-1beta / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016848:Naegleria fowleri / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases