Escherichia coli aggravates endoplasmic reticulum stress and triggers CHOP-dependent apoptosis in weaned pigs

Abstract

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 (21 days old) were randomly assigned to one of two treatment groups (n = 9 per group). After pre-feeding for 1 week, the diets of the piglets in one group were supplemented with E. coli (W25 K, 10 cells kg diet) for 7 days. 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.

Protective effect of FBXL10 in myocardial ischemia reperfusion injury via inhibiting endoplasmic reticulum stress

“…The GRP78, the major ER-resident chaperone, is well known as a biomarker of ERs in the course of disease [19,20]. If sustained ERs persisted, inflammatory and apoptotic pathways are activated, including the induction of CHOP, PERK, caspase-3, caspase-12 and NF-κB [21][22][23]. It has been reported that overexpression of CHOP led to apoptosis after ERs and participated in ERs related diseases [24].…”

Copper Induces Apoptosis Through Endoplasmic Reticulum Stress in Skeletal Muscle of Broilers

“…In the early stages of UPR, the endoplasmic reticulum activates various transcriptional programs to enhance its protein folding capacity and cellular stress associated with reduced endoplasmic reticulum when the adaptive warning effect is produced [35]. For a prolonged period, the endoplasmic reticulum mediates apoptosis by activating transcription factors such as the CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP/GADD153), Caspase-12, and the JNKdependent pathway [36,37]. CHOP is a specific transcription factor of ERS, which can be induced by IRE1, ATF6, and eIF2α, and finally activates Caspase3 to induce apoptosis.…”

Genome-Wide Phylogenetic Analysis, Expression Pattern, and Transcriptional Regulatory Network of the Pig C/EBP Gene Family

“… 18 The C/EBPζ gene regulates endoplasmic reticulum stress-mediated apoptosis which has been found in many tissues of pigs. 19 - 24 But the expression pattern of C/EBP gene family in pigs’ tissues also has not been systematically analyzed.…”