1. Neuromedin U elicits cytokine release in murine Th2-type T cell clone D10.G4.1.
- Author
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Johnson EN, Appelbaum ER, Carpenter DC, Cox RF, Disa J, Foley JJ, Ghosh SK, Naselsky DP, Pullen MA, Sarau HM, Scheff SR, Steplewski KM, Zaks-Zilberman M, and Aiyar N
- Subjects
- Animals, Calcineurin physiology, Calcium metabolism, Cell Line, Clone Cells, Cytokines antagonists & inhibitors, Dogs, Estrenes pharmacology, Humans, Interleukins antagonists & inhibitors, Interleukins metabolism, MAP Kinase Signaling System immunology, Membrane Proteins biosynthesis, Membrane Proteins genetics, Mice, Mitogen-Activated Protein Kinases metabolism, Neuropeptides metabolism, Phosphatidylinositol 3-Kinases physiology, Pyrrolidinones pharmacology, Rats, Receptors, Interleukin-4 physiology, Receptors, Neurotransmitter biosynthesis, Receptors, Neurotransmitter genetics, Signal Transduction immunology, Swine, Type C Phospholipases antagonists & inhibitors, Type C Phospholipases physiology, Cytokines metabolism, Membrane Proteins physiology, Neuropeptides physiology, Receptors, Neurotransmitter physiology, Th2 Cells immunology, Th2 Cells metabolism
- Abstract
Neuromedin U (NmU), originally isolated from porcine spinal cord and later from other species, is a novel peptide that potently contracts smooth muscle. NmU interacts with two G protein-coupled receptors designated as NmU-1R and NmU-2R. This study demonstrates a potential proinflammatory role for NmU. In a mouse Th2 cell line (D10.G4.1), a single class of high affinity saturable binding sites for (125)I-labeled NmU (K(D) 364 pM and B(max) 1114 fmol/mg protein) was identified, and mRNA encoding NmU-1R, but not NmU-2R, was present. Competition binding analysis revealed equipotent, high affinity binding of NmU isopeptides to membranes prepared from D10.G4.1 cells. Exposure of these cells to NmU isopeptides resulted in an increase in intracellular Ca(2+) concentration (EC(50) 4.8 nM for human NmU). In addition, NmU also significantly increased the synthesis and release of cytokines including IL-4, IL-5, IL-6, IL-10, and IL-13. Studies using pharmacological inhibitors indicated that maximal NmU-evoked cytokine release required functional phospholipase C, calcineurin, MEK, and PI3K pathways. These data suggest a role for NmU in inflammation by stimulating cytokine production by T cells.
- Published
- 2004
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