downstream gene activation of the receptor alx by the agonist annexin a1下游基因的激活受体受体激动剂膜联蛋白a1 alx.pdfVIP

Downstream Gene Activation of the Receptor ALX by the Agonist Annexin A1 1. 1. 1 1 Derek Renshaw , Trinidad Montero-Melendez , Jesmond Dalli , Ahmad Kamal , Vincenzo 1,2 1 2 1 Brancaleone , Fulvio D’Acquisto , Giuseppe Cirino , Mauro Perretti * 1 William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom, 2 Department of Experimental Pharmacology, School of Pharmacy, University of Naples, Naples, Italy Abstract Background: Our understanding of pro-resolution factors in determining the outcome of inflammation has recently gained ground, yet not many studies have investigated whether specific genes or patterns of genes, are modified by these mediators. Here, we have focussed on the glucocorticoid modulated pro-resolution factor annexin A1 (AnxA1), studying if its interaction with the ALX receptor would affect downstream genomic targets. Methodology/Principal Findings: Using microarray technology in ALX transfected HEK293 cells, we discovered an over- lapping, yet distinct gene activation profile for AnxA1 compared to its N-terminal mimetic peptide Ac2-26, which may be suggestive of unique downstream inflammatory outcomes for each substance. When the up-regulated genes were explored, consistently induced was the sphingosine phosphate phosphatase-2 gene (SGPP2), involved in regulation of the sphingosine 1 phosphate chemotactic system. Up-regulation of this gene, as well as JAG1 (and down-regulation of JAM3), was confirmed using real time PCR both with transfected