Escherichia coli aggravates endoplasmic reticulum stress and triggers CHOP-dependent apoptosis in weaned pigs.
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Intestinal cells can sense the presence of pathogens and trigger many important signaling pathways to maintain tissue homeostasis and normal function. Escherichia coli and lipopolysaccharides (LPS) are the main pathogenic factors of intestinal disease in pigs. However, the roles of endoplasmic reticulum stress (ERS) and its mediated apoptosis in intestinal malfunction induced by E. coli or LPS remain unclear. In the present study, we aimed to evaluate whether ERS could be activated by E. coli fed to piglets and whether the underlying mechanisms of this disease process could be exploited. Eighteen weaned pigs (21days old) were randomly assigned to one of two treatment groups (n=9 per group). After pre-feeding for 1week, the diets of the piglets in one group were supplemented with E. coli (W25K, 109 cells kg-1 diet) for 7days. At the end of the experiment, all piglets were slaughtered to collect jejunum and ileum samples. Western blotting and immunofluorescence experiments were used to determine the expression levels and histological locations of ERS and its downstream signaling proteins. The intestinal porcine epithelial cell line J2 (IPEC-J2) was used as in vitro model to investigate the possible mechanism. The results showed that E. coli supplementation in the diet increased the GRP78 expression in the jejunum and ileum, especially in the jejunal epithelium and ileac germinal center, and elevated the expression levels of CHOP (in both the jejunum and ileum) and caspase-11 (in the ileum), indicating that ERS and CHOP-caspase-11 dependent apoptosis were activated in the porcine small intestine. Moreover, as demonstrated by in vitro experiments, the CHOP inhibitor 4-phenylbutyrate alleviated the damage to IPEC-J2 cells induced by LPS derived from E. coli. Taken together, these data strongly suggest that ERS can be triggered in the small intestine by dietary supplementation with E. coli and that CHOP-caspase-11 dependent apoptosis may play a key role in maintaining normal homeostasis of the intestine in response to pathogenic factors.
author list (cited authors)
Jiang, Q., Chen, S., Ren, W., Liu, G., Yao, K., Wu, G., & Yin, Y.
complete list of authors
Jiang, Qian||Chen, Shuai||Ren, Wenkai||Liu, Gang||Yao, Kang||Wu, Guoyao||Yin, Yulong