Interleukin-6 changes tight junction permeability and intracellular phospholipid content in a human enterocyte cell culture model.
Proinflammatory cytokines and secretory phospholipase A(2) (sPLA(2)) are elevated in patients with inflammatory bowel disease (IBD). We previously reported that the proinflammatory cytokine IL-6 increased the expression of sPLA(2) (a hydrolyzer of phosphatidylcholine) and decreased membrane integrity in an intestinal epithelial cell culture model. To determine the physiological effects of the IL-6 mediated increase in sPLA(2) on decreased epithelial layer integrity, we investigated alterations of intracellular/secretory phospholipid (PL) composition in a cell culture model. In addition, since other PLs may also mediate epithelial membrane activity, we investigated the effect of IL-6 on PL activity in a Caco-2 enterocyte culture model. Caco-2 cells were incubated for 72 h with IL-6 or media alone (control). Both media and cell lysate were analyzed for PL composition using thin-layer chromatography. The PL composition in the media did not show any differences between the two groups ( p>0.1). Total intracellular PL contents were also unchanged; however, IL-6 led to significant changes in PL composition including an increase in phosphatidylethanolamine (PE) and sphingomyelin (SM) and a decrease in phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) ( p<0.05). Both PE and SM are known as inflammatory signaling factors involved in human IBD. Our study suggests that the decreased membrane integrity seen with IL-6 application may occur via intracellular PL alterations, rather than through the direct effects of sPLA(2).
Section of Pediatric Surgery, University of Michigan Medical School, F3970 Mott Children's Hospital, Ann Arbor, MI 48109-0245, USA.
Y
Y
Tazuke
R A
RA
Drongowski
D H
DH
Teitelbaum
A G
AG
Coran
D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D020895:Enterocytes; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D042541:Intracellular Space; D010743:Phospholipids / Q000378:metabolism*; D019108:Tight Junctions / Q000187:drug effects*
D015850:Interleukin-6; D010743:Phospholipids