Copper
(Cu) is a common additive in food products, which poses
a potential concern to animal and human health when it is in excess.
Here, we investigated the relationship between endoplasmic reticulum
(ER) stress and pyroptosis in Cu-induced toxicity of jejunum in vivo and in vitro. In in vivo experiments, excess intake of dietary Cu caused ER cavity expansion,
elevated fluorescence signals of GRP78 and Caspase-1, and increased
the mRNA and protein expression levels related to ER stress and pyroptosis
in pig jejunal epithelium. Simultaneously, similar effects were observed
in IPEC-J2 cells under excess Cu treatment. Importantly, 4-phenylbutyric
acid (ER stress inhibitor) and MKC-3946 (IRE1α inhibitor) significantly
inhibited the ER stress-triggered IRE1α-XBP1 pathway, which
also alleviated the Cu-induced pyroptosis in IPEC-J2 cells. In general,
these results suggested that ER stress participated in regulating
Cu-induced pyroptosis in jejunal epithelial cells via the IRE1α-XBP1 pathway, which provided a novel view into the
toxicology of Cu.