Effects of Calcineurin Inhibitors on Intestinal Barrier in Caco-2 Cells

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Calcineurin inhibitors (tacrolimus/FK506, cyclosporin A/CsA) are immunosuppressants with known gastrointestinal side effects like mucosal damage.
• The direct impact of these drugs on intestinal epithelial cells (IECs) has not been fully established.

Purpose of the Study:

• To investigate whether calcineurin inhibitors directly damage intestinal epithelial cells and compromise the intestinal barrier function.

Main Methods:

• Utilized Caco-2 cells, a human intestinal cell line, to model the intestinal barrier.
• Assessed the effects of FK506, CsA, and deltamethrin on tight junction protein expression (zonula occludens-1) and cell permeability (using Lucifer Yellow).

Main Results:

• Calcineurin inhibitors significantly inhibited zonula occludens-1 expression in confluent Caco-2 cells.
• Treatment with these drugs led to increased intestinal permeability in confluent cells.
• These detrimental effects were not clearly observed in subconfluent cell cultures.

Conclusions:

• Calcineurin inhibitors can exert direct cytotoxic effects on intestinal epithelial cells.
• These drugs compromise the intestinal barrier integrity by disrupting tight junctions and increasing permeability, particularly in confluent monolayers.