Regulator of G-protein signaling 4 suppresses LPS-induced MUC5AC overproduction in the airway.
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.
Song
Kyoung Seob
KS
The Airway Mucus Institute, Yonsei University College of Medicine, Seoul 120-752, Korea.
Kim
Hyun Jun
HJ
Kim
Kyubo
K
Lee
Jeung Gweon
JG
Yoon
Joo-Heon
JH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000737:chemistry; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
D008070:Lipopolysaccharides; C524678:MUC5AC protein, human; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; C546385:P2RY2 protein, human; C546386:P2ry2 protein, mouse; D020710:RGS Proteins; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C098799:RGS4 protein; D000255:Adenosine Triphosphate; D043802:GTP-Binding Protein alpha Subunits, Gq-G11