
pmid: 19059885
Mucus overproduction and airway obstruction are common features in airway mucosal inflammation. The mechanism by which LPS induces MUC5AC overexpression, however, has not been fully explored. The aims of this study were twofold: first, to examine the ATP-dependent mechanism by which LPS induces MUC5AC gene expression, and second, to identify specific molecules that could suppress LPS-induced MUC5AC expression at a G-protein-coupled receptor level. Here, we suggest that LPS from Pseudomonas aeruginosa induces MUC5AC overproduction by both an ATP-dependent pathway and an ATP-independent pathway. In addition, we showed that Regulator of G-protein signaling (RGS) 4 plays as a suppressor for ATP-induced MUC5AC expression by interacting with G alpha q in a GTP-dependent manner in vivo. These results give additional insights into the molecular mechanism of negative regulation of mucin overproduction and enhance our understanding of mucus hypersecretion during airway mucosal inflammation.
Lipopolysaccharides, Time Factors, Adenosine Triphosphate/metabolism, Mucin 5AC/genetics, RGS4, Respiratory Mucosa/pathology, Messenger/metabolism, Mucin 5AC, Inbred C57BL, Receptors, Purinergic P2Y2, Mice, Adenosine Triphosphate, Epithelial Cells/pathology, RGS Proteins/genetics, Receptors, Cells, Cultured, Mice, Knockout, Cultured, Gq-G11/metabolism, Respiratory Mucosa/drug effects*, lipopolysaccharide, Nasal Mucosa/drug effects, Epithelial Cells/metabolism, GTP-Binding Protein alpha Subunits, Up-Regulation, Mucin 5AC/metabolism*, Respiratory Mucosa/metabolism, Pseudomonas aeruginosa, RGS Proteins/metabolism*, 570, Cells, Knockout, Epithelial Cells/drug effects*, Respiratory Mucosa, Lipopolysaccharides/pharmacology*, Purinergic P2/drug effects, Transfection, P2Y2, Toll-Like Receptor 4/drug effects, Animals, Humans, RNA, Messenger, Purinergic P2Y2, Lipopolysaccharides/isolation & purification, Pseudomonas aeruginosa/chemistry, Metaplasia, Purinergic P2/metabolism, Receptors, Purinergic P2, Epithelial Cells, MUC5AC, Nasal Mucosa/metabolism, ATP, Mice, Inbred C57BL, Nasal Mucosa, Toll-Like Receptor 4/metabolism, RNA, GTP-Binding Protein alpha Subunits, Gq-G11, RGS Proteins/deficiency, RGS Proteins
Lipopolysaccharides, Time Factors, Adenosine Triphosphate/metabolism, Mucin 5AC/genetics, RGS4, Respiratory Mucosa/pathology, Messenger/metabolism, Mucin 5AC, Inbred C57BL, Receptors, Purinergic P2Y2, Mice, Adenosine Triphosphate, Epithelial Cells/pathology, RGS Proteins/genetics, Receptors, Cells, Cultured, Mice, Knockout, Cultured, Gq-G11/metabolism, Respiratory Mucosa/drug effects*, lipopolysaccharide, Nasal Mucosa/drug effects, Epithelial Cells/metabolism, GTP-Binding Protein alpha Subunits, Up-Regulation, Mucin 5AC/metabolism*, Respiratory Mucosa/metabolism, Pseudomonas aeruginosa, RGS Proteins/metabolism*, 570, Cells, Knockout, Epithelial Cells/drug effects*, Respiratory Mucosa, Lipopolysaccharides/pharmacology*, Purinergic P2/drug effects, Transfection, P2Y2, Toll-Like Receptor 4/drug effects, Animals, Humans, RNA, Messenger, Purinergic P2Y2, Lipopolysaccharides/isolation & purification, Pseudomonas aeruginosa/chemistry, Metaplasia, Purinergic P2/metabolism, Receptors, Purinergic P2, Epithelial Cells, MUC5AC, Nasal Mucosa/metabolism, ATP, Mice, Inbred C57BL, Nasal Mucosa, Toll-Like Receptor 4/metabolism, RNA, GTP-Binding Protein alpha Subunits, Gq-G11, RGS Proteins/deficiency, RGS Proteins
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