title: Zearalenone mycotoxin affects immune mediators, MAPK signalling molecules, nuclear receptors and genome-wide gene expression in pig spleen.
abstract: The toxicity of zearalenone (ZEA) was evaluated in swine spleen, a key organ for the innate and adaptative immune response. Weaned pigs were fed for 18 days with a control or a ZEA contaminated diet. The effect of ZEA was assessed on wide genome expression, pro- (TNF-α, IL-8, IL-6, IL-1β, IFN-γ) and anti-inflammatory (IL-10, IL-4) cytokines, other molecules involved in inflammatory processes (MMPs/TIMPs), as well as signaling molecules, (p38/JNK1/JNK2-MAPKs) and nuclear receptors (PPARγ/NFkB/AP-1/STAT3/c-JUN). Microarray analysis showed that 46% of total number of differentially expressed genes was involved in cellular signaling pathway, 13% in cytokine network and 10% in the inflammatory response. ZEA increased expression and synthesis of pro- inflammatory (TNF-α, IL-8, IL-6, IL-1β) and had no effect on IFN-γ, IL-4 and IL-10 cytokines in spleen. The inflammatory stimulation might be a consequence of JNK pathway activation rather than of p-38MAPK and NF-kB involvement whose gene and protein expression were suppressed by ZEA action. In summary, our findings indicated the role of ZEA as an immune disruptor at spleen level.
authors.affiliation: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, 077015, Balotesti, Ilfov, Romania.
authors.forename: Gina Cecilia
authors.initials: GC
authors.lastname: Pistol
authors.affiliation: Oncologic Institute Prof. Dr. I. Chiricuta, 400015, Cluj-Napoca, Romania; Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400565, Cluj-Napoca, Romania.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Braicu
authors.affiliation: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, 077015, Balotesti, Ilfov, Romania.
authors.forename: Monica
authors.initials: M
authors.lastname: Motiu
authors.affiliation: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, 077015, Balotesti, Ilfov, Romania.
authors.forename: Mihail Alexandru
authors.initials: MA
authors.lastname: Gras
authors.affiliation: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, 077015, Balotesti, Ilfov, Romania.
authors.forename: Daniela Eliza
authors.initials: DE
authors.lastname: Marin
authors.affiliation: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, 077015, Balotesti, Ilfov, Romania.
authors.forename: Mariana
authors.initials: M
authors.lastname: Stancu
authors.affiliation: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, 077015, Balotesti, Ilfov, Romania.
authors.forename: Loredana
authors.initials: L
authors.lastname: Calin
authors.affiliation: Biotechnology Department, University of Agriculture and Veterinary Medicine, 011464, Bucharest, Romania.
authors.forename: Florentina
authors.initials: F
authors.lastname: Israel-Roming
authors.affiliation: Oncologic Institute Prof. Dr. I. Chiricuta, 400015, Cluj-Napoca, Romania; Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400565, Cluj-Napoca, Romania; Department of Experimental Therapeutics M.D. Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
authors.affiliation: Laboratory of Animal Biology, National Institute for Research and Development for Biology and Animal Nutrition, 077015, Balotesti, Ilfov, Romania.
authors.forename: Ionelia
authors.initials: I
authors.lastname: Taranu
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009183:Mycotoxins / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D013552:Swine; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D007155:Immunologic Factors; D007378:Interleukins; D009183:Mycotoxins; D016328:NF-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D015025:Zearalenone; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases