@article{mbs:/content/journal/micro/10.1099/mic.0.030635-0, author = "Cervantes-Sandoval, Isaac and Serrano-Luna, José de Jesús and Meza-Cervantez, Patricia and Arroyo, Rossana and Tsutsumi, Víctor and Shibayama, Mineko", title = "Naegleria fowleri induces MUC5AC and pro-inflammatory cytokines in human epithelial cells via ROS production and EGFR activation", journal= "Microbiology", year = "2009", volume = "155", number = "11", pages = "3739-3747", doi = "https://doi.org/10.1099/mic.0.030635-0", url = "https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.030635-0", publisher = "Microbiology Society", issn = "1465-2080", type = "Journal Article", keywords = "IL-8, interleukin-8", keywords = "FDA, 2,7-dichlorofluorescein diacetate", keywords = "PAM, primary amoebic meningoencephalitis", keywords = "CCL11, chemokine c-c motif ligand 11", keywords = "ROS, reactive oxygen species", keywords = "TNF-α, tumour necrosis factor-α", keywords = "EGFR, epidermal growth factor receptor", keywords = "PMA, phorbol 12-myristate 13-acetate", keywords = "IL-1β, interleukin-1β", keywords = "GAPDH, glyceraldehyde-3-phosphate dehydrogenase", keywords = "CNS, central nervous system", keywords = "MUC5AC, mucin 5AC", keywords = "TGF-α, transforming growth factor-α", abstract = " Naegleria fowleri is an amoeboflagellate responsible for the fatal central nervous system (CNS) disease primary amoebic meningoencephalitis (PAM). This amoeba gains access to the CNS by invading the olfactory mucosa and crossing the cribriform plate. Studies using a mouse model of infection have shown that the host secretes mucus during the very early stages of infection, and this event is followed by an infiltration of neutrophils into the nasal cavity. In this study, we investigated the role of N. fowleri trophozoites in inducing the expression and secretion of airway mucin and pro-inflammatory mediators. Using the human mucoepidermal cell line NCI-H292, we demonstrated that N. fowleri induced the expression of the MUC5AC gene and protein and the pro-inflammatory mediators interleukin-8 (IL-8) and interleukin-1β (IL-1β), but not tumour necrosis factor-α or chemokine c-c motif ligand 11 (eotaxin). Since the production of reactive oxygen species (ROS) is a common phenomenon involved in the signalling pathways of these molecules, we analysed if trophozoites were capable of causing ROS production in NCI-H292 cells by detecting oxidation of the fluorescent probe 2,7-dichlorofluorescein diacetate. NCI-H292 cells generated ROS after 15–30 min of trophozoite stimulation. Furthermore, the expression of MUC5AC, IL-8 and IL-1β was inhibited in the presence of the ROS scavenger DMSO. In addition, the use of an epidermal growth factor receptor inhibitor decreased the expression of MUC5AC and IL-8, but not IL-1β. We conclude that N. fowleri induces the expression of some host innate defence mechanisms, such as mucin secretion (MUC5AC) and local inflammation (IL-8 and IL-1β) in respiratory epithelial cells via ROS production and suggest that these innate immune mechanisms probably prevent most PAM infections.", }