HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murthy, S. Articles by Field, F. J. Search for Related Content PubMed PubMed Citation Articles by Murthy, S. Articles by Field, F. J. Social Bookmarking                      What's this?

J Biol Chem, Vol. 275, Issue 13, 9222-9229, March 31, 2000

Tumor Necrosis Factor- and Interleukin-1 Inhibit Apolipoprotein B Secretion in CaCo-2 Cells via the Epidermal Growth Factor Receptor Signaling Pathway^*

Shubha Murthy, Satya N. Mathur, and F. Jeffrey Field

From the Department of Internal Medicine and Veterans Affairs, University of Iowa, Iowa City, Iowa 52242

In inflammatory conditions of the gut, cytokines are released into the mucosa and submucosa propagating and sustaining the inflammatory response. In CaCo-2 cells, we have shown that various inflammatory cytokines interfere with the secretion of lipids, an effect that is likely caused by the release of a ligand to the epidermal growth factor (EGF) receptor. In the present study, the role of the EGF receptor signaling pathway and the effects of the cytokines tumor necrosis factor- (TNF-) and and interleukin 1 (IL-1) on triacylglycerol-rich lipoprotein secretion were investigated. CaCo-2 cells were incubated with oleic acid to enhance triacylglycerol-rich lipoprotein secretion. TNF- and IL-1 significantly decreased the basolateral secretion of apolipoprotein B (apoB) mass, with IL-1 being more potent. Tyrphostin, an inhibitor of the EGF receptor intrinsic tryosine kinase, prevented or markedly attenuated the decrease in apoB secretion by TNF- or IL-1. Both cytokines increased the phosphorylation of the EGF receptor by 30 min. Moreover, phosphotyrosine immunoblots of the EGF receptor demonstrated an increase in tyrosine residues phosphorylated by 0.5 and 6.5 h. At both these time points, TNF- and IL-1 also decreased the binding of EGF to its cell surface receptor. At 6.5 h, activation of the EGF receptor was sustained. In contrast, the early activation of the receptor was only transient as receptor phosphorylation and binding of EGF to its receptor returned to basal levels by 2 h. Preventing ligand binding to the EGF receptor by a receptor-blocking antibody attenuated receptor activation observed after 6.5 h. This did not occur at 0.5 h, suggesting that early activation of the EGF receptor was non-ligand-mediated. Similarly, apoB secretion was inhibited by an early non-ligand-mediated process; whereas at the later time, inhibition of apoB secretion was ligand-mediated. Thus, the inflammatory cytokines TNF- and IL-1 interfere with the secretion of triacylglycerol-rich lipoproteins by both early and delayed signaling events mediated by the EGF receptor signaling pathway.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Hevi and S. L. Chuck Ferritins Can Regulate the Secretion of Apolipoprotein B J. Biol. Chem., August 22, 2003; 278(34): 31924 - 31929. [Abstract] [Full Text] [PDF]

				R. M. Hobbs and F. M. Watt Regulation of Interleukin-1{alpha} Expression by Integrins and Epidermal Growth Factor Receptor in Keratinocytes from a Mouse Model of Inflammatory Skin Disease J. Biol. Chem., May 23, 2003; 278(22): 19798 - 19807. [Abstract] [Full Text] [PDF]

				K. Singh, O. A. Batuman, H. O. Akman, M. H. Kedees, V. Vakil, and M. M. Hussain Differential, Tissue-specific, Transcriptional Regulation of Apolipoprotein B Secretion by Transforming Growth Factor beta J. Biol. Chem., October 11, 2002; 277(42): 39515 - 39524. [Abstract] [Full Text] [PDF]

				R. Hemi, K. Paz, N. Wertheim, A. Karasik, Y. Zick, and H. Kanety Transactivation of ErbB2 and ErbB3 by Tumor Necrosis Factor-alpha and Anisomycin Leads to Impaired Insulin Signaling through Serine/Threonine Phosphorylation of IRS Proteins J. Biol. Chem., March 8, 2002; 277(11): 8961 - 8969. [Abstract] [Full Text] [PDF]