Aims
Lipopolysaccharides (LPSs) act as virulence factors that trigger intestinal inflammation and thereby compromise the production of pigs worldwide. Intestinal diseases and dysfunction have been attributed to endoplasmic reticulum stress (ERS) and the subsequent apoptosis of intestinal epithelial cells. Therefore It is important to explore whether LPSs aggravate ERS-mediated apoptosis of intestinal epithelial cells.
Background/aims
Lipopolysaccharides (LPSs) act as virulence factors that trigger intestinal inflammation and thereby compromise the production of pigs worldwide. Intestinal diseases and dysfunction have been attributed to endoplasmic reticulum stress (ERS) and the subsequent apoptosis of intestinal epithelial cells. Therefore It is important to explore whether LPSs aggravate ERS-mediated apoptosis of intestinal epithelial cells.
Conclusion
This novel finding implies that intestinal malfunctions might solely originate from the effects of Gram-negative bacteria on ERS-responsive intestinal cells. The regulation of ERS signaling (especially the crosstalk between nuclear GRP78 and p53) in ERS-responsive/rapidly growing intestines may help intestinal cells survive from Gram-negative bacterial infections.
Methods
ERS and inflammation models were established in porcine cell line J2 (IPEC-J2) and the cells were treated with tunicamycin or LPS at specific times. The expression of marker proteins was determined by western blot and immunofluorescence. Possible crosstalk between proteins was analyzed by co-immunoprecipitation. Small interfering RNA transfection was employed to verify the mechanisms.
Results
We found that Escherichia coli-derived LPS aggravated ERS and ERS-mediated apoptosis in ERS-responsive IPEC-J2 cells. The crosstalk between nuclear glucose-regulated protein 78 (GRP78) and tumor protein 53 (p53) was verified to trigger this LPS-aggravated apoptosis of ERS-responsive intestinal cells.