Differential effect of ethanol and hydrogen peroxide on barrier function and prostaglandin E2 release in differentiated Caco-2 cells: Selective prevention by growth factors
✍ Scribed by Rose-Marie Catalioto; Carla Festa; Antonio Triolo; Maria Altamura; Carlo Alberto Maggi; Sandro Giuliani
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 304 KB
- Volume
- 98
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
The present study investigates the effects of ethanol and hydrogen peroxide (H 2 O 2 ) on the barrier function and prostaglandin E 2 (PGE 2 ) release in differentiated Caco-2 cells. Epithelial barrier integrity was estimated by measuring transepithelial electrical resistance (TEER), the transport of reference compounds and lactate dehydrogenase leakage, the PGE 2 release by enzyme immunoassay. Ethanol and H 2 O 2 decreased TEER and increased the transport of lucifer yellow without affecting that of propranolol and phenylalanine. Only the effects of ethanol were accompanied by PGE 2 production and were reversible without causing long-term cytotoxicity. The cyclooxygenase-2 inhibitor, NS-398, prevented the effect of ethanol on both PGE 2 release and TEER, while inhibition of both cyclooxygenase-2 and tyrosine kinase drastically compromised cell viability and TEER recovery. Hepatocyte growth factor, keratinocyte growth factor or insulin prevented the effect of ethanol on cell permeability, but not on PGE 2 release. Their combination prevented the effect of H 2 O 2 . In conclusion, ethanol and H 2 O 2 increased paracellular permeability in differentiated Caco-2 cells without affecting transcellular and active transport. Cyclooxygenase-2 stimulated PGE 2 release mediated the reversible effect of ethanol on tight junctions and, meanwhile, contributed to cell survival. Growth factors, normally present in the intestine, exerted a selective protective effect toward paracellular permeability increase induced by irritants.