title: Cytotoxicity and immunotoxicity of cyclopiazonic acid on human cells.
abstract: In this study, in vitro cytotoxicity and immunotoxicity of the mycotoxin cyclopiazonic acid (CPA) was evaluated on human cells. To evaluate cytoxicity, several cellular targets were used (CD34+, monocytes, THP-1 and Caco-2). Monocytes were more sensitive to CPA than the THP-1 monocytic cell line after 48h of incubation in the tested conditions. Half maximal inhibitory concentration (IC50) were determined to be 8.5 × 10(-8) and 1.75 × 10(-7)M for monocytes and THP1, respectively, while IC50>1.25 × 10(-7)M was observed for Caco-2 and CD34+ cells. The CPA effect on macrophage differentiation was also examined at non-cytotoxic concentrations. The monocyte differentiation process was markedly disturbed in the presence of CPA. After 6 days of culture, CD71 expression was downregulated, while CD14 and CD11a expressions did not change. Moreover, activated macrophages showed a raised burst activity and TNF-α secretion. Overall, the results indicated that CPA exhibited toxicity on various human cellular models. Moreover, at non-cytotoxic concentrations, CPA disturbed human monocytes differentiation into macrophages. This work contributes to understanding the immunosuppressive properties of this food-related toxin.
authors.affiliation: Université de Brest, EA3882, Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, SFR ScInBioS, ESIAB, Technopôle de Brest Iroise, 29280 Plouzané, France. Electronic address: nolwenn.hymery@univ-brest.fr.
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Hymery
authors.affiliation: Université de Brest, EA3882, Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, SFR ScInBioS, ESIAB, Technopôle de Brest Iroise, 29280 Plouzané, France.
authors.forename: Floriane
authors.initials: F
authors.lastname: Masson
authors.affiliation: Université de Brest, EA3882, Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, SFR ScInBioS, ESIAB, Technopôle de Brest Iroise, 29280 Plouzané, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Barbier
authors.affiliation: Université de Brest, EA3882, Laboratoire Universitaire de Biodiversité et d'Ecologie Microbienne, SFR ScInBioS, ESIAB, Technopôle de Brest Iroise, 29280 Plouzané, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Coton
mesh_terms: D018952:Antigens, CD34; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007211:Indoles / Q000633:toxicity*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009183:Mycotoxins / Q000633:toxicity*; D016897:Respiratory Burst / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D007211:Indoles; D009183:Mycotoxins; D014409:Tumor Necrosis Factor-alpha; C000543:cyclopiazonic acid
keywords: Cyclopiazonic acid; Food contaminant; Human cells; Immunotoxicity; Mycotoxin; Toxicity