ATP significantly increases P2Y2-dependent RANTES secretion and overexpression in human airway epithelial cells

Abstract

Uncontrolled inflammation is frequently observed in human respiratory diseases. Extracellular ATP can induce a number of physiological phenomena via binding to purinergic receptors. In spite of the fact that ATP has long been known as a proinflammatory mediator in the airway, the signaling pathway mechanism is still unclear. Here we show that ATP increases RANTES secretion and overexpression in a time-dependent manner and siRNA-P2Y2 significantly decreases RANTES secretion and overexpression. These results suggest that ATP can induce secretion and overexpression of the RANTES chemokine via a P2Y2 Gαq coupled receptor-dependent manner. In addition, pharmacological inhibition of ERK1/2 MAPK by U0126 suppressed ATP/P2Y2-induced RANTES overexpression in the human airway epithelium. These results show that RANTES secretion and overexpression are regulated by a P2Y2 receptor and the ATP/P2Y2 signaling complex may be critical for airway inflammation in respiratory diseases. Taken together, our investigation provides novel insight into the physiological functions of the P2Y2 receptor and enhances our understanding of the inflamed microenvironment in the airway.