title: Cry1Ac toxin induces macrophage activation via ERK1/2, JNK and p38 mitogen-activated protein kinases.
abstract: The Cry1Ac toxin from Bacillus thuringiensis is used commercially as a bio-insecticide and is expressed in transgenic plants that are used for human and animal consumption. Although it was originally considered innocuous for mammals, the Cry1Ac toxin is not inert and has the ability to induce mucosal and systemic immunogenicity. Herein, we examined whether the Cry1Ac toxin promotes macrophage activation and explored the signalling pathways that may mediate this effect. Treatment of primary and RAW264.7 macrophages with the Cry1Ac toxin resulted in upregulation of the costimulatory molecules CD80, CD86 and ICOS-L and enhanced production of nitric oxide, the chemokine MCP-1 and the proinflammatory cytokines TNF-α and IL-6. Remarkably, the Cry1Ac toxin induced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK1/2, JNK and p38 and promoted nuclear translocation of nuclear factor-kappa B (NF-κB) p50 and p65. p38 and ERK1/2 MAPKs were involved in this effect, as indicated by the Cry1Ac-induced upregulation of CD80 and IL-6 and TNF-α abrogation by the p38 MAPK inhibitor SB203580. Furthermore, treatment the MEK1/2 kinase inhibitor PD98059 blocked increases in MCP-1 secretion and augmented Cry1Ac-induced ICOS-L upregulation. These data demonstrate the capacity of the Cry1Ac toxin to induce macrophage activation via the MAPK and NF-κB pathways.
authors.affiliation: Laboratorio de Inmunidad en Mucosas, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, Mexico.
authors.forename: Marilu
authors.initials: M
authors.lastname: Torres-Martínez
authors.affiliation: Laboratorio de Inmunidad en Mucosas, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, Mexico.
authors.forename: Néstor
authors.initials: N
authors.lastname: Rubio-Infante
authors.affiliation: Laboratorio de Inmunidad en Mucosas, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, Mexico.
authors.forename: Ana Lilia
authors.initials: AL
authors.lastname: García-Hernández
authors.affiliation: Laboratorio de Inmunidad en Mucosas, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, Mexico.
authors.forename: Raúl
authors.initials: R
authors.lastname: Nava-Acosta
authors.affiliation: Laboratorio de Inmunidad en Mucosas, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, Mexico.
authors.forename: Damaris
authors.initials: D
authors.lastname: Ilhuicatzi-Alvarado
authors.affiliation: Laboratorio de Inmunidad en Mucosas, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, Mexico. Electronic address: lemofi@unam.mx.
authors.forename: Leticia
authors.initials: L
authors.lastname: Moreno-Fierros
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D006460:Hemolysin Proteins / Q000633:toxicity*; D015850:Interleukin-6 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004731:Endotoxins; D006460:Hemolysin Proteins; D015850:Interleukin-6; D052002:NF-kappa B p50 Subunit; D009573:Nitrites; D047428:Protein Kinase Inhibitors; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C030956:insecticidal crystal protein, Bacillus Thuringiensis; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Bacillus thuringiensis; Cry1Ac toxin; MAPK pathways; Macrophage activation