Journal of Lipid Research, Vol 38, 206-216, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Inhibition of apolipoprotein B secretion by IL-6 is mediated by EGF or an EGF-like molecule in CaCo-2 cells

S Murthy, S Mathur, WP Bishop and EJ Field
Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.

Small intestinal mucosal inflammation observed in celiac disease is associated with the local release of growth factors and various cytokines. In a previous study, we investigated the effect of various cytokines on triacylglycerol and apoB secretion by CaCo-2 cells and observed that TNF-alpha, IL-1 beta, and particularly IL-6, decreased apolipoprotein (apo) B and triacylglycerol secretion. In this study, we explored possible mechanisms to explain the inhibitory effect of IL-6 on apoB secretion. IL-6, 10 ng/mL, added to the basolateral medium of CaCo-2 cells grown on semi-permeable filters, decreased apoB secretion by 42%. Adding a blocking monoclonal antibody (mAb 528) to the EGF receptor completely prevented this effect. IL-6 decreased the amount of EGF receptor protein and the binding of iodinated EGF to its receptor by 50% and 30%, respectively. Incubation of cells with various ligands to the EGF receptor, such as EGF, TGF-alpha, HB-EGF, and amphiregulin, also decreased apoB secretion. Inhibition of apoB secretion by EGF was prevented by the mAb 528 or an EGF neutralizing antibody. In a dose- dependent manner, the neutralizing antibody to EGF prevented the decrease in secretion of apoB, triacylglycerol mass, and cell-surface binding of labeled EGF caused by IL-6. Similar to the effects of IL-6, EGF decreased the secretion of triacylglycerol mass and the synthesis and secretion on newly synthesized apoB. The results suggest that, in CaCo-2 cells, IL-6 causes the release of EGF or an EGF-like molecule. By binding to cell surface EGF receptors, the molecule then causes a decrease in triacylglycerol and apoB secretion.
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