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Characterization of in vitro effects of patulin on intestinal epithelial and immune cells

2016-04Journal article Restricted access
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dc.contributor.authorAssunção, Ricardo
dc.contributor.authorAlvito, Paula
dc.contributor.authorKleiveland, C.R.
dc.contributor.authorLea, T.E.
dc.date.accessioned2016-08-10T10:54:05Z
dc.date.available2020-05-01T00:30:12Z
dc.date.issued2016-04
dc.description.abstractThe intestinal mucosa is the first biological barrier encountered by natural toxins, and could possibly be exposed to high amounts of dietary mycotoxins. Patulin (PAT), a mycotoxin produced by Penicillium spp. during fruit spoilage, is one of the best known enteropathogenic mycotoxins able to alter functions of the intestine (Maresca et al., 2008). This study evaluated the effects of PAT on barrier function of the gut mucosa utilizing the intestinal epithelial cell model Caco-2, and scrutinized immunomodulatory effects using human peripheral blood mononuclear cells (PBMC) and human blood monocyte-derived dendritic cells (moDCs) as test systems. PAT exposure reduced Caco-2 cell viability at concentrations above 12 mM. As expected, the integrity of a polarized Caco-2 monolayer was affected by PAT exposure, as demonstrated by a decrease in TER values, becoming more pronounced at 50 mM. No effects were detected on the expression levels of the tight junction proteins occludin, claudin-1 and claudin-3 at 50 mM. However, the expression of zonula occludens-1 (ZO-1) and myosin light chain 2 (MLC2) declined. Also, levels of phospho-MLC2 (p-MLC2) increased after 24 h of exposure to 50 mM of PAT. T cell proliferation was highly sensitive to PAT with major effects for concentrations above 10 nM of PAT. The same conditions did not affect the maturation of moDC. PAT causes a reduction in Caco-2 barrier function mainly by perturbation of ZO-1 levels and the phosphorylation of MLC. Low doses of PAT strongly inhibited T cell proliferation induced by a polyclonal activator, but had no effect on the maturation of moDC. These results provide new information that strengthens the concept that the epithelium and immune cells of the intestinal mucosa are important targets for the toxic effects of food contaminants like mycotoxinspt_PT
dc.description.sponsorshipThis research was developed on behalf of a Short Term Scientific Mission within the Infogest COST action and supported by the project Mycomix (PTDC/DTP-FTO/0417/2012) and through CESAM (UID/AMB/50017/2013) both funded by the Fundação para a Ciência e Tecnologia, (Portugal) and the Department of Chemistry, Biotechnology and Food Science of the Norwegian University of Life Sciences.pt_PT
dc.identifier.citationToxicol Lett. 2016 May 27;250-251:47-56. doi: 10.1016/j.toxlet.2016.04.007. Epub 2016 Apr 8pt_PT
dc.identifier.issn0378-4274
dc.identifier.urihttp://hdl.handle.net/10400.18/3910
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/EUROTOXpt_PT
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0378427416300571pt_PT
dc.subjectPatulinpt_PT
dc.subjectIntestinal mucosapt_PT
dc.subjectTight junctionspt_PT
dc.subjectPhosphorylationpt_PT
dc.subjectImmune effectspt_PT
dc.subjectPatulinapt_PT
dc.subjectMicotoxinaspt_PT
dc.subjectSegurança Alimentarpt_PT
dc.subjectToxicologiapt_PT
dc.subjectAvaliação de Riscopt_PT
dc.subjectSaúde Humanapt_PT
dc.titleCharacterization of in vitro effects of patulin on intestinal epithelial and immune cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F0417%2F2012/PT
oaire.citation.endPage56pt_PT
oaire.citation.startPage47pt_PT
oaire.citation.titleToxicology Letterspt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication7dee8a4a-7112-45ce-a8cb-8c552d7ae061
relation.isProjectOfPublication.latestForDiscovery7dee8a4a-7112-45ce-a8cb-8c552d7ae061

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