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.