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The P2Y14 Receptor of Airway Epithelial Cells

Coupling to Intracellular Ca²⁺ and IL-8 Secretion

Department of Pneumology, University of Freiburg; Department of Pneumology, University of Rostock; Department of Dermatology, University of Jena; Wilhelm-Anton-Hospital, Goch, Germany; and Department of Experimental and Diagnostic Medicine, Section of General Pathology and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Italy

Correspondence and requests for reprints should be addressed to Dr. Marco Idzko, Department of Pneumology, University Medical Clinic, University of Freiburg, D-79104 Freiburg i. Br., Germany. E-mail: idzko{at}med1.ukl.uni-freiburg.de

Uridine nucleotides and UDP-glucose are endogenous molecules, which are released into the extracellular environment in a lytic manner after cell damage, as well as by regulated nonlytic mechanisms. Recently, a UDP-glucose–specific G_i protein–coupled P2Y receptor, namely P2Y₁₄, has been cloned. In this study, we demonstrated expression of the P2Y₁₄ mRNA in human lung epithelial cells and in the epithelial cell lines A549 and BEAS-2B. Evidence of functional expression of the P2Y₁₄ receptor in these cell lines was provided by calcium measurements after stimulation with uridine 5'-diphosphoglucose (UDP-glc). Experiments with pertussis toxin and the Ca²⁺-chelator EGTA revealed participation of pertussis toxin–sensitive G_i/o-proteins in the mobilization of Ca²⁺-ions from intracellular stores by UDP-glc. Moreover, UDP-glc increased secretion of the potent neutrophil chemoattractant CXCL8/IL-8 in A549 and BEAS-2B cells in a pertussis toxin–sensitive manner. Moreover, reverse transcription and quantitative polymerase chain reaction revealed that UDP-glc modulated mRNA levels of IL-8/CXCL8. However, stimulation of A549 and BEAS-2B cells with UDP-glc neither modified basal nor cytokine-induced secretion of the CXC-chemokines CXCL9/MIG, CXCL10/IP-10, and CXCL11/I-TAC. In addition, UDP-glc did not affect proliferation of the two cell lines. In summary, our data provide evidence for a distinct physiologic role of P2Y₁₄ in the selective release of specific chemokines from human airway epithelial cells.

Key Words: airway • epithelial cells • P2Y₁₄ • purinoceptors • UDP-glucose

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