Van De Walle, Jacqueline
[UCL]
(eng)
Deoxynivalenol (DON, vomitoxin), the most prevalent trichothecene
mycotoxin worldwide, contaminates numerous food items from cereal
origin. DON adversely affects animal health with symptoms going from
reduced nutritional efficiency and weight gain upon chronic low dose
exposure, to emesis, leukocytosis and haemorrhage upon acute high level
ingestion. Also human toxicoses related to DON ingestion have been
reported.
The gastro-intestinal tract is the primary site of DON exposure in terms of
timing and amount, and could constitute both a target of and a barrier to
DON toxicity. The objective of this research was to determine the impact of
DON exposure on inflammatory parameters in human intestinal epithelial
cells in vitro.
Proliferating and differentiated Caco-2 cells, respectively representative of
young/immature, and adult/mature human enterocytes were exposed to
realistic intestinal concentrations of DON (50 to 5000 ng/ml) during 24h.
The induction of intracellular inflammatory signalling pathways was
observed through the activation of the Mitogen Activated Protein Kinases
(ERK1/2, JNK and p38) and the transcription factor Nuclear Factor (NF)-
κB. DON dose-dependently upregulated the production of the inflammatory
mediators IL-8 and PGE-2. These phenomena occurred similarly in
proliferating and differentiated cells and were dependent on ERK1/2, JNK
and NF-κB activation. The simultaneous exposure to a mixture of
inflammatory mediators (IL-1β, TNF-α, IFN-γ and LPS) representative of an
acute inflammatory reaction caused synergic increases in IL-8 secretion.
Continuous incubation with DON (50 ng/ml) during 21 days increased basal
level of IL-8 and PGE-2 production.
DON exposure furthermore caused a dose-dependent increase of the
paracellular permeability of the Caco-2 monolayer together with a decrease
in protein synthesis, with a possible link between these events being the
diminished synthesis of the tight junction protein claudin-4. Also intestinal
alkaline phosphatase expression, a marker of cellular differentiation, was
reduced.
The results of this research allow to conclude that DON induces
inflammatory parameters in the intestinal epithelium, together with causing a
weakening of the monolayer structure and functioning. These observations
could be important for human health hazard evaluation regarding DON
exposure.
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Bibliographic reference |
Van De Walle, Jacqueline. Deoxynivalenol and intestinal inflammation : an in vitro assessment. Prom. : Larondelle, Yvan ; Schneider, Yves-Jacques |
Permanent URL |
http://hdl.handle.net/2078.1/28810 |