title: GRO-α/CXCR2 system and ADAM17 correlated expression in Sjögren's syndrome.
abstract: The chemokine GRO-α and its receptor CXCR2 are associated with the chronic inflammation in Sjögren's syndrome (SS). To better understand the molecular mechanisms by which the GRO-α/CXCR2 system is involved in the SS inflammatory condition, our studies were designed to clarify the role of ADAM17 activation in the modulation of the GRO-α/CXCR2 chemokine system in epithelial cells (SGEC) from SS salivary glands. The CXCR2 overexpression observed in SS SGEC was dramatically decreased by ADAM17 inhibitor TAPI-1. In addition, comparing the expression levels of ADAM17 in healthy SGEC in presence or not of GRO-α treatment, we observed that GRO-α dose-dependently influences ADAM17 activation, an effect that was inhibited by blocking the interaction of GRO-α with its CXCR2 receptor. Our data show for the first time that ADAM17 has an important role in GRO-α/CXCR2 system activity regulation, suggesting that regulating CXCR2/ADAM17 interaction could be an attractive therapeutic target in SS.
authors: Department of Basic Medical Sciences, Section of Human Anatomy and Histology, Laboratory of Cell Biology, University of Bari Medical School, Bari, Italy. sabrina.lisi@uniba.it
authors: Sabrina
authors: S
authors: Lisi
authors: Margherita
authors: M
authors: Sisto
authors: Dario Domenico
authors: DD
authors: Lofrumento
authors: Massimo
authors: M
authors: D'Amore
authors: Raffaella
authors: R
authors: De Lucro
authors: Domenico
authors: D
authors: Ribatti
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D000072198:ADAM17 Protein; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000096:biosynthesis / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007249:Inflammation; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis / Q000378:metabolism*; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000276:immunology / Q000378:metabolism*
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D004151:Dipeptides; D006877:Hydroxamic Acids; C092152:N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; D023063:Receptors, Interleukin-8B; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
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