title: Sublethal doses of dinophysistoxin-1 and okadaic acid stimulate secretion of inflammatory factors on innate immune cells: Negative health consequences.
abstract: One of the proposed mechanisms to explain why Diarrhetic Shellfish Poison (DSP) toxins are tumor promoters is founded on the capacity of these toxins to increase TNF-α secretion. Although macrophages are the principal cells in the activation of the inflammatory response, the immune profile that Okadaic acid (OA) and Dinophysistoxin-1 (DTX-1) trigger in these cells has not been fully explored. We have therefore investigated the effect of various concentrations of both toxins on the activity of several inflammatory factors. Our results demonstrate that OA and DTX-1, at sublethal doses, stimulate secretion of inflammatory factors. Nevertheless DTX-1 was more potent than OA in increasing TNF-α and IL-6 as well as their dependent chemokines KC, MCP-1, LIX, MIP-1 α, MIP-1 β and MIP-2. On the other hand, secretion of IFN-γ and the anti-inflammatory cytokines, IL-4 and IL-10, was unaffected. In addition, DTX-1 also raises matrix metalloproteinase-9 (MMP-9) activity. In this study, for the first time the effect of OA and DTX-1 over the secretion of pro-inflammatory and carcinogenic signals in macrophages are compared, showing that DTX-1 is ten times more potent that OA. The inflammatory profile produced by DTX-1 is shown for the first time. The safe limit regulation should be changed to DSP toxins zero tolerance in the shellfish to be consumed by humans.
authors.affiliation: Laboratorio de Bioquímica de Membrana, Programa de Fisiología y Biofísica, Facultad de Medicina, Universidad de Chile, Independencia 1027, Correo 7, Santiago 8380000, Chile; Fundación Ciencia y Tecnología para el Desarrollo (FUCITED), Edo. Castillo Velasco 2902, Santiago 7750269, Chile. Electronic address: miguel.delcampo@fucited.cl.
authors.forename: Miguel
authors.initials: M
authors.lastname: Del Campo
authors.affiliation: Fundación Ciencia y Tecnología para el Desarrollo (FUCITED), Edo. Castillo Velasco 2902, Santiago 7750269, Chile. Electronic address: t.zhonghu@fucited.cl.
authors.forename: Ta-Ying
authors.initials: TY
authors.lastname: Zhong
authors.affiliation: Fundación Ciencia y Tecnología para el Desarrollo (FUCITED), Edo. Castillo Velasco 2902, Santiago 7750269, Chile. Electronic address: ricardo.tampe@fucited.cl.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Tampe
authors.affiliation: Centro Avanzado de Enfermedades Crónicas (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Olivos 1007, Santiago 8380492, Chile. Electronic address: logarcia@ciq.uchile.cl.
authors.forename: Lorena
authors.initials: L
authors.lastname: García
authors.affiliation: Laboratorio de Bioquímica de Membrana, Programa de Fisiología y Biofísica, Facultad de Medicina, Universidad de Chile, Independencia 1027, Correo 7, Santiago 8380000, Chile. Electronic address: nlagos@med.uchile.cl.
authors.forename: Néstor
authors.initials: N
authors.lastname: Lagos
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019319:Okadaic Acid / Q000633:toxicity* / Q000031:analogs & derivatives; D011714:Pyrans / Q000633:toxicity*; D018675:Toxicity Tests; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D011714:Pyrans; D014409:Tumor Necrosis Factor-alpha; D019319:Okadaic Acid; C051904:dinophysistoxin 1
keywords: Dinophysistoxin-1; Okadaic acid; Pro-inflammatory immune responses