The expression of urotensin II receptor (U2R) is up-regulated by interferon-gamma.
Urotensin-II (U-II) was identified as the natural ligand of the G protein-coupled receptor GPR14, which has been correspondingly renamed Urotensin-II receptor (U2R). The tissue distribution of U2R and the pharmacological effects of U-II suggest a novel neurohormonal system with potent cardiovascular effects. We here report the human rhabdomyosarcoma cell line TE-671 as the first natural and endogenous source of functional U2R in an immortalized cell line. In TE-671 cells, U-II stimulated extracellular signal regulated kinase phosphorylation and increased c-fos mRNA expression. Furthermore, we demonstrate that the expression of U2R mRNA and functional U-II high affinity binding sites are serum-responsive and that they are specifically up-regulated by interferon gamma (IFNgamma). We propose that IFNgamma contributes to the previously observed increase of U2R density in the heart tissue of congestive heart failure (CHF) patients and we suggest that U2R up-regulation, as a consequence of an inflammatory response, could lead to a clinical worsening of this disease.
Birker-Robaczewska
Magdalena
M
Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
Boukhadra
Céline
C
Studer
Rolf
R
Mueller
Célia
C
Binkert
Christoph
C
Nayler
Oliver
O
D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D015854:Up-Regulation
D016207:Cytokines; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D007371:Interferon-gamma; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases