This Article Full Text Full Text (PDF) All Versions of this Article: 2008-0280OCv1 41/1/40    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Song, K. S. Articles by Yoon, J.-H. PubMed PubMed Citation Articles by Song, K. S. Articles by Yoon, J.-H.

Regulator of G-Protein Signaling 4 Suppresses LPS-Induced MUC5AC Overproduction in the Airway

¹ The Airway Mucus Institute, ² Department of Otorhinolaryngology, and ³ Brain Korea 21 for Medical Sciences, ⁴ Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Korea; and ⁵ Department of Otolaryngology, Ajou University College of Medicine, Suwon, Korea

Correspondence and requests for reprints should be addressed to Joo-Heon Yoon, M.D., Ph.D., Department of Otorhinolaryngology, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752, Korea. E-mail: jhyoon{at}yuhs.ac

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 Gq 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.

Key Words: lipopolysaccharide • ATP • MUC5AC • P2Y₂ • RGS4

CLINICAL RELEVANCE This work gives additional insights into the molecular mechanism of negative regulation of mucin overproduction and enhances our understanding of mucus hypersecretion during airway mucosal inflammation.