scholarly journals Intestinal Epithelial Cell Exosome Launches IL-1β-Mediated Neuron Injury in Sepsis-Associated Encephalopathy

2022 ◽  
Vol 11 ◽  
Author(s):  
Shaosong Xi ◽  
Yunguang Wang ◽  
Chenghao Wu ◽  
Weihua Peng ◽  
Ying Zhu ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Fecal Microbiota Transplantation ◽  
Intestinal Flora ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
M1 Polarization ◽  
16S Rna ◽  
Neuron Injury

BackgroundGut–microbiota–brain axis links the relationship between intestinal microbiota and sepsis-associated encephalopathy (SAE). However, the key mediators between them remain unclear.MethodsMemory test was determined by Water maze. Intestinal flora was measured by 16S RNA sequencing. Neurotransmitter was detected by high-performance liquid chromatography (HPLC). Histopathology was determined by H&E, immunofluorescence (IF), and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. Flow cytometry was employed to determine the proportion of macrophages.ResultsFecal microbiota transplantation (FMT) relieved hippocampus impairment of SAE rats by inhibiting inflammation cytokine secretion, the expression of IBA-1 and neurotransmitter disturbance, and cell apoptosis and autophagy, accompanied by the reduced M1 polarization and M1 pro-inflammation factors produced by macrophages in mesenteric lymph nodes (MLNs). Actually, M1 polarization in SAE rats depended on intestinal epithelial cell (IEC)-derived exosome. GW4869-initiated inhibition of exosome secretion notably abolished M1 polarization and the secretion of IL-1β. However, GW4869-mediated improvement of hippocampus impairment was counteracted by the delivery of recombinant interleukin (IL)-1β to hippocampus. Mechanistically, IEC-derived exosome induced the excessive circulating IL-1β produced by CP-R048 macrophages, which subsequently induced damage and apoptosis of hippocampal neurons H19-7 in an autophagy-dependent manner. And reactivation of autophagy facilitates intestinal IL-1β-mediated hippocampal neuron injury.ConclusionCollectively, intestinal flora disturbance induced the exosome release of IECs, which subsequently caused M1 polarization in MLNs and the accumulation of circulating IL-1β. Circulating IL-1β promoted the damage and apoptosis of neurons in an autophagy-dependent manner. Possibly, targeting intestinal flora or IEC-derived exosome contributes to the treatment of SAE.

fMLP induces Hsp27 expression, attenuates NF-κB activation, and confers intestinal epithelial cell protection

2007 ◽  
Vol 292 (4) ◽  
pp. G1070-G1078 ◽  
Author(s):  
Ryan M. Carlson ◽  
Stephan R. Vavricka ◽  
Jyrki J. Eloranta ◽  
Mark W. Musch ◽  
Donna L. Arvans ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Target Genes ◽  
Bacterial Flora ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Cell Protection ◽  
Hsp27 Expression ◽  
Tnf Α

Sustained expression of cytoprotective intestinal epithelial heat shock proteins (Hsps), particularly Hsp27, depends on stimuli derived from bacterial flora. In this study, we examined the role of the bacterial chemotactic peptide fMLP in stimulating colonic epithelial Hsp expression at concentrations encountered in a physiological milieu. Treatment of the polarized human intestinal epithelial cell line Caco2bbe with physiological concentrations of fMLP (10–100 nM) induced expression of Hsp27, but not Hsp72, in a time- and concentration-dependent manner. Induction of Hsp27 by fMLP was specific since the fMLP analogs MRP and MLP were not effective. Hsp27 induction by fMLP was blocked by the fMLP-receptor antagonist BOC-FLFLF and was blocked when the dipeptide transporter PepT1, an entry pathway for fMLP, was silenced. fMLP activated both the p38 and ERK1/2 MAP kinase pathways in Caco2bbe cells, but not the SAPK/JNK pathway. The p38 inhibitor SB203580, but not the MEK-1 inhibitor PD98059, blocked Hsp27 induction by fMLP. fMLP treatment inhibited actin depolymerization and decreased transepithelial resistance caused by the oxidant monochloramine, and this inhibition was reversed by silencing Hsp27 expression. fMLP pretreatment also inhibited activation of proinflammatory transcription factor NF-κB by TNF-α in Caco2bbe cells, reducing induction of NF-κB target genes by TNF-α both in human intestinal biopsies and Caco2bbe cells. In conclusion, fMLP may contribute to the maintenance of intestinal homeostasis by mediating physiological expression of Hsp27, enhancing cellular protection, and negatively regulating the inflammatory response.

Phospholipase A2 stimulation of rat intestinal epithelial cell (IEC-6) migration

1996 ◽  
Vol 271 (4) ◽  
pp. G664-G668
Author(s):  
T. Minami ◽  
S. Zushi ◽  
Y. Shinomura ◽  
Y. Matsuzawa
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Phospholipase A2 ◽  
Intestinal Epithelial Cell ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Lipoxygenase Inhibitor ◽  
Promoting Effect ◽  
Epithelial Cell Migration

The effect of phospholipase A2 (PLA2) on intestinal epithelial cell migration was investigated using an in vitro wounding model of confluent monolayers of IEC-6. PLA2 (0.001-2 U/ml) enhanced IEC-6 cell migration in a dose dependent manner. Addition of 4-bromophenacyl bromide (BPB) (a PLA2 inhibitor) to PLA2 completely blocked the migration-promoting effect. However, addition of piroxicam (a cyclooxygenase inhibitor) or nordihydroguaiaretic acid (a lipoxygenase inhibitor) had no influence on the effect. Lysophosphatidylcholine (lysoPC) (0.01-5,000 ng/ml), one of the products of phosphatidylcholine by PLA2, dose-dependently enhanced IEC-6 cell migration as well. A combination of PsLA2 (1 U/ml) and lysoPC (1,000 ng/ml) had no additive effect or migration. Moreover, the migration-promoting effect of PLA2 that was blocked by BPB was recovered by lysoPC. After pretreatment of IEC-6 cells with replication-inhibiting doses of mitomycin C, the enhanced migration induced by PLA2 or lysoPC was still observed. These observations suggest that PLA2 may, independently of proliferation, enhance intestinal epithelial cell migration mainly via lysoPC.

Intestinal epithelial cell transported TLR2 ligand stimulates Ly6C+ monocyte differentiation in a G-CSF dependent manner

Immunobiology ◽  
2015 ◽  
Vol 220 (11) ◽  
pp. 1255-1265 ◽  
Author(s):  
Ida H. Hiemstra ◽  
Kim Vrijland ◽  
Marye M. Hogenboom ◽  
Gerd Bouma ◽  
Georg Kraal ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Monocyte Differentiation ◽  
Tlr2 Ligand
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