title: Excretory and Secretory Proteins of Naegleria fowleri Induce Inflammatory Responses in BV-2 Microglial Cells.
abstract: Naegleria fowleri, a free-living amoeba that is found in diverse environmental habitats, can cause a type of fulminating hemorrhagic meningoencephalitis, primary amoebic meningoencephalitis (PAM), in humans. The pathogenesis of PAM is not fully understood, but it is likely to be primarily caused by disruption of the host's nervous system via a direct phagocytic mechanism by the amoeba. Naegleria fowleri trophozoites are known to secrete diverse proteins that may indirectly contribute to the pathogenic function of the amoeba, but this factor is not clearly understood. In this study, we analyzed the inflammatory responses in BV-2 microglial cells induced by excretory and secretory proteins of N. fowleri (NfESP). Treatment of BV-2 cells with NfESP induced the expression of various cytokines and chemokines, including the proinflammatory cytokines IL-1α and TNF-α. NfESP-induced IL-1α and TNF-α expression in BV-2 cells were regulated by p38, JNK, and ERK MAPKs. NfESP-induced IL-1α and TNF-α production in BV-2 cells were effectively downregulated by inhibition of NF-kB and AP-1. These results collectively suggest that NfESP stimulates BV-2 cells to release IL-1α and TNF-α via NF-kB- and AP-1-dependent MAPK signaling pathways. The released cytokines may contribute to inflammatory responses in microglia and other cell types in the brain during N. fowleri infection.
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, 52727, Korea.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, 52727, Korea.|BK21Plus Team for Anti-aging Biotechnology and Industry, Department of Convergence Medical Science, Gyeongsang National University, Jinju, 52727, Korea.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Kang
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, 52727, Korea.
authors.forename: Tae Im
authors.initials: TI
authors.lastname: Kim
authors.affiliation: Department of Parasitology, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Korea.
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Suwon, 16499, Korea.|Department of Biomedical Science, Ajou University School of Medicine, Suwon, 16499, Korea.
authors.forename: Hae-Jin
authors.initials: HJ
authors.lastname: Sohn
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, 52727, Korea.|BK21Plus Team for Anti-aging Biotechnology and Industry, Department of Convergence Medical Science, Gyeongsang National University, Jinju, 52727, Korea.
authors.forename: Byoung-Kuk
authors.initials: BK
authors.lastname: Na
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Suwon, 16499, Korea.|Department of Biomedical Science, Ajou University School of Medicine, Suwon, 16499, Korea.
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Shin
mesh_terms: D000656:Amoeba / Q000472:pathogenicity; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020808:Central Nervous System Protozoal Infections / Q000276:immunology / Q000469:parasitology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016848:Naegleria fowleri / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism*; D053058:Trophozoites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D018925:Chemokines; D016207:Cytokines; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D016328:NF-kappa B; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: AP-1; MAPK; NF-kB; cytokines