Faculty Collaboration Database

Human intestinal epithelial cells express receptors for platelet-activating factor. Am J Physiol 1999 Oct;277(4):G810-8

Date

10/12/1999

Pubmed ID

10516147

DOI

10.1152/ajpgi.1999.277.4.G810

Scopus ID

2-s2.0-0032699565 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

The intestinal epithelium produces and responds to cytokines and lipid mediators that play a key role in the induction and regulation of mucosal inflammation. The lipid mediator platelet-activating factor (PAF) can be produced and degraded by the human intestinal epithelium and is known to mediate a range of proinflammatory and other biological effects in the intestinal mucosa. In the studies herein, we assessed whether or not human intestinal epithelial cells express cell surface or intracellular PAF receptors (PAF-R), whether expression of these receptors can be regulated, and whether human intestinal epithelial cells respond to PAF. Several human colon epithelial cell lines (HT-29, Caco-2, T84, HCT-8, HCA-7, I407, and LS-174T) were shown by RT-PCR to constitutively express mRNA for PAF-R. In addition, PAF-R expression was demonstrated by immunoblot analysis and PAF-R was shown to be constitutively expressed on the cell surface of several of these cell lines, as assessed by flow cytometry. PAF-R expression by human colon epithelial cells was upregulated by stimulation with retinoic acid but not by stimulation with PAF, proinflammatory agonists (tumor necrosis factor-alpha, interleukin-1, interferon-gamma), or transforming growth factor-alpha. PAF-R on intestinal epithelial cells were functional, as PAF stimulation of the cells increased tyrosine phosphorylation of several cellular proteins, including proteins of 75 and 125 kDa, and this response was blocked by a PAF-R antagonist. Consistent with the findings using cell lines, PAF-R were also constitutively expressed by normal human colon and small intestinal epithelium in vivo, as shown by immunohistology. The constitutive and regulated expression of functional PAF-R by human intestinal epithelium suggests PAF produced by the intestinal epithelial cells or cells underlying the epithelium has autocrine or paracrine effects on intestinal epithelial cells.

Author List

Merendino N, Dwinell MB, Varki N, Eckmann L, Kagnoff MF

Author

Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Line
Cell Membrane
Colon
Humans
Immunoblotting
Intestinal Mucosa
Intestine, Small
Phosphorylation
Platelet Activating Factor
Platelet Membrane Glycoproteins
RNA, Messenger
Receptors, Cell Surface
Receptors, G-Protein-Coupled
Tyrosine