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Human intestinal epithelial cells express receptors for platelet-activating factor
N Merendino1, M B Dwinell, N Varki
1Department of Medicine, University of California San Diego, La Jolla, California 92093-0623, USA.
The American Journal of Physiology
|October 12, 1999
Summary
Human intestinal cells express functional platelet-activating factor receptors (PAF-R). Their expression can be regulated, suggesting PAF signaling influences intestinal inflammation.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- The intestinal epithelium plays a crucial role in mucosal inflammation by producing and responding to various mediators.
- Platelet-activating factor (PAF) is a lipid mediator known to induce proinflammatory effects in the intestinal mucosa.
- Understanding PAF's role requires investigating its interaction with intestinal epithelial cells.
Purpose of the Study:
- To determine if human intestinal epithelial cells express platelet-activating factor receptors (PAF-R).
- To assess the regulation of PAF-R expression.
- To investigate the functional response of intestinal epithelial cells to PAF.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) to detect PAF-R mRNA.
- Immunoblot analysis and flow cytometry to confirm PAF-R expression on cell surfaces.
- Stimulation assays with retinoic acid, PAF, and other agonists to study receptor regulation and function, including tyrosine phosphorylation analysis.
Main Results:
- Multiple human colon epithelial cell lines constitutively express PAF-R mRNA and protein.
- PAF-R are constitutively expressed on the cell surface of intestinal epithelial cells in vitro and in vivo.
- Retinoic acid upregulates PAF-R expression, while PAF and other inflammatory mediators do not.
- PAF stimulation triggers functional responses, including protein tyrosine phosphorylation, mediated by PAF-R.
Conclusions:
- Human intestinal epithelial cells express functional PAF-R.
- PAF-R expression is constitutive and can be regulated, notably by retinoic acid.
- These findings suggest autocrine or paracrine roles for PAF in regulating intestinal epithelial cell function and potentially mucosal inflammation.