Published ahead of print on September 8, 2005, doi:10.1165/rcmb.2004-0220RC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 6, December 2005, 523-530 A more recent version of this article appeared on December 1, 2005
Submitted on July 12, 2004 Differential Regulation of MUC5AC/Muc5ac and hCLCA-1/Gob-5 Expression in Airway EpitheliumPhilip Thai1,1 Center for Comparative Respiratory Biology and Medicine, University of California at Davis, Davis, CA, USA, 2 Department of Internal Medicine, University of California at San Francisco, San Francisco, CA, USA * To whom correspondence should be addressed. E-mail: rwu{at}ucdavis.edu.
This study demonstrates that the two biomarkers, MUC5AC/Muc5ac and hCLCA1/Gob5, that are frequently associated with surface mucous/goblet cells in asthmatic airways are differentially regulated. Intratracheal instillation of IL13 (0.5 µg/mouse lung) elicited 8 and 110 fold induction of Muc5ac and Gob5 messages, respectively within 24 hrs in wild type mouse lung, while these inductions were abrogated in Stat6 knock out mice. The induction of MUC5AC/Muc5ac message could not be duplicated in vitro with primary tracheobronchial epithelial (TBE) cells derived from wild type mice or humans, despite significant inductions still seen for hCLCA1/Gob5. Further studies with JAK inhibitors and STAT6 signaling showed active signaling of the JAK/STAT6 pathway in these primary TBE cultures by IL13 in the regulation of hCLCA1 expression. Dual immunofluorescent staining with antibodies specific to MUC5AC and hCLCA1 revealed a differential nature of the expression of these two biomarkers by distinct cell types of primary TBE cultures. Finally, MUC5AC expression could be elevated by a bacterial product, peptidoglycan, without any induction of hCLCA1. Thus, these results suggest that the two biomakers of the metaplastic airway mucous cell type are differentially regulated by JAK/STAT6-dependent and independent pathways.
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