The P2Y14 receptor of airway epithelial cells: coupling to intracellular Ca2+ and IL-8 secretion.
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 P2Y(14), has been cloned. In this study, we demonstrated expression of the P2Y(14) mRNA in human lung epithelial cells and in the epithelial cell lines A549 and BEAS-2B. Evidence of functional expression of the P2Y(14) receptor in these cell lines was provided by calcium measurements after stimulation with uridine 5'-diphosphoglucose (UDP-glc). Experiments with pertussis toxin and the Ca(2+)-chelator EGTA revealed participation of pertussis toxin-sensitive G(i/o)-proteins in the mobilization of Ca(2+)-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 P2Y(14) in the selective release of specific chemokines from human airway epithelial cells.
Müller
Tobias
T
Department of Pneumology, University Medical Clinic, University of Freiburg, D-79104 Freiburg i. Br., Germany. idzko@med1.ukl.uni-freiburg.de
Bayer
Hans
H
Myrtek
Daniel
D
Ferrari
Davide
D
Sorichter
Stephan
S
Ziegenhagen
Manfred W
MW
Zissel
Gernot
G
Virchow
J Christian
JC
Luttmann
Werner
W
Norgauer
Johannes
J
Di Virgilio
Francesco
F
Idzko
Marco
M
D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058470:Receptors, Purinergic P2Y; D020545:Respiratory Mucosa / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
D002118:Calcium; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D004533:Egtazic Acid; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D037342:Pertussis Toxin; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2; D058470:Receptors, Purinergic P2Y; D014532:Uridine Diphosphate Glucose; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C518528:P2Y14 receptor, human