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).
Tazuke
Y
Y
Section of Pediatric Surgery, University of Michigan Medical School, F3970 Mott Children's Hospital, Ann Arbor, MI 48109-0245, USA.
Drongowski
R A
RA
Teitelbaum
D H
DH
Coran
A G
AG
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