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Am J Physiol Cell Physiol (November 27, 2002). doi:10.1152/ajpcell.00507.2001
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Articles in PresS, published online ahead of print November 27, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00507.2001
Submitted on October 22, 2001
Accepted on November 21, 2002

Lateral Membrane Lipoxin A4 Receptors Mediate LXA4'sAnti-inflammatory Actions on Intestinal Epithelium

Torsten Kucharzik1, Andrew T Gewirtz1, Didier Merlin1, James L Madara1, and Ifor R Williams1*

1 Pathology, Emory University, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: irwilli{at}emory.edu.

Lipoxin A4 (LXA4), and its stable analogs down-regulate chemokine secretion in polarized epithelia. This anti-inflammatory effect has been suggested to be mediated by the LXA4 receptor (LXA4R), a G protein-coupled receptor. To determine whether LXA4R was expressed on the apical, basolateral, or both poles of intestinal epithelia, an N-terminal c-myc epitope tag was added to the human LXA4R cDNA and recombinant retroviruses utilized to transduce polarized epithelial cells. In polarized T84 intestinal epithelial cells, c-myc-LXA4R was preferentially expressed on the basolateral surface as indicated by cell surface selective biotinylation and confocal microscopy. Further, expression of c-myc-LXA4R and a truncation mutant lacking the cytoplasmic terminus was primarily confined to the lateral subdomain. Lastly, we observed that the expression of c-myc-LXA4 conferred enhanced down-regulation of IL-8 expression in response to LXA4 analog and that blockade of the CysLT1 receptor by montelukast did not prevent this response to LXA4 analog. Thus, LXA4 generated in or near the paracellular space via neutrophil-epithelial interactions can rapidly act on epithelial LXA4R to down-regulate epithelial promotion of intestinal inflammation.




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