Viral dsRNA activates mucin transcription in airway epithelial cells.
Double-stranded (ds) RNA is a biologically active component of many viruses including rhinoviruses infecting the upper respiratory tract. Mucus production is a common symptom of such infections. Here, we show that mucin, the glycoprotein subunit of mucus gels, is transcriptionally upregulated in an NF-kappaB- and p38-dependent manner when homogeneous cultures of epithelial cells are exposed to dsRNA. Furthermore, upstream of p38 in this system, dsRNA stimulates the extracellular release of ATP and activation of cell surface ATP receptors, which are G protein-coupled. This results in the stimulation of phospholipase C and protein kinase C. These findings suggest that ATP receptor antagonists could be used to modulate mucus production induced by virus.
Londhe
Vedang
V
Biomedical Sciences Program, Cardiovascular Research Institute, Department of Anatomy, University of California, San Francisco 94143-0452, USA.
McNamara
Nancy
N
Lemjabbar
Hassan
H
Basbaum
Carol
C
D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012367:RNA, Viral / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D019892:eIF-2 Kinase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011956:Receptors, Cell Surface; D019892:eIF-2 Kinase; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D020962:Heterotrimeric GTP-Binding Proteins