Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone

Abstract

A mucus layer coats the gastrointestinal tract and serves as the first line of intestinal defense against infection. N-acyl-homoserine lactone (AHL) quorum-sensing molecules produced by gram-negative bacteria in the gut can influence the homeostasis of intestinal epithelium. In this study, we investigated the effects of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on cell viability and mucus secretion in LS174T cells. C12-HSL but not C4-HSL significantly decreased cell viability by inducing mitochondrial dysfunction and activating cell apoptosis which led to a decrease in mucin expression. Pretreatment with lipid raft disruptor (Methyl-β-cyclodextrin, MβCD) and oxidative stress inhibitor (N-acetyl-L-cysteine, NAC) slightly rescued the viability of cells damaged by C12-HSL exposure, while the paraoxonase 2 (PON2) inhibitor (Triazolo[4,3-a]quinolone, TQ416) significantly affected recovering cells viability and mucin secretion. When LS174T cells were treated with C12-HSL and TQ416 simultaneously, TQ416 showed the maximal positive effect on cells viability. However, if cells were first treated with C12-HSL for 40 mins, and then TQ46 was added, the TQ416 had no effect on cell viability. These results suggest that the C12-HSL-acid process acts at an early step to activate apoptosis as part of C12-HSL’s effect on intestinal mucus barrier function.

Original low birth weight deteriorates the hindgut epithelial barrier function in pigs at the growing stage

“…Our data revealed that the number of goblet cells in the colonic and caecal epithelia of LBW pigs was significantly lower than that of the normal group, which was consistent with the previous study in a mouse model (44). Deletion of intestinal goblet cells inhibited the synthesis and secretion of mucin, which affected the function of the intestinal chemical barrier (45). Our data demonstrated that the mRNA expression of mucin 2 was significantly reduced in the colonic and caecal mucosa of LBW pigs, whereas the mRNA abundances of mucin 1, 4, 13, and 20 did not change between NBW and LBW pigs.…”

Icariin and its phosphorylated derivatives alleviate intestinal epithelial barrier disruption caused by enterotoxigenic Escherichia coli through modulate p38 MAPK in vivo and in vitro

“…26 Briefly, after the culture medium was removed, the cells were washed 3 times with PBS. 26 Briefly, after the culture medium was removed, the cells were washed 3 times with PBS.…”

“…Mitochondrial ROS in IPEC-J2 cells were measured with MitoSox red mitochondrial superoxide indicator (Invitrogen) as described previously. 26 Briefly, after the culture medium was removed, the cells were washed 3 times with PBS. MitoSox red mitochondrial superoxide indicator, diluted to a final concentration of 4 mM with serum-free DMEM, was added to the cells and incubated for 20 minutes at 37°C in the dark.…”

Bacteria-Host Crosstalk: Sensing of the Quorum in the Context of <b><i>Pseudomonas aeruginosa</i></b> Infections

“…The P. aeruginosa 3O-C 12 -HSL also influences mitochondrial physiology [113, 114] by depolarizing the membrane potential and releasing mitochondrial cytochrome C into the cytosol; it was concluded that 3O-C 12 -HSL has a pro-apoptotic effect via activating caspases 3/7 and 8 without the involvement of Bak/Bax [114]. Indeed, it appears to trigger apoptosis in certain types of cells, such as mouse and human fibroblasts, monocyte-, and neutrophil-like tumor cell lines [115].…”