Abstract
This study demonstrates that the two biomarkers, MUC5AC/ Muc5ac and hCLCA1/Gob5, which are frequently associated with surface mucous/goblet cells in asthmatic airways, are differentially regulated. Intratracheal instillation of IL-13 (0.5 mug/mouse lung) elicited 8- and 110-fold induction of Muc5ac and Gob5 messages, respectively, within 24 h in wild-type mouse lung, whereas these inductions were abrogated in Stat6 knockout 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 IL-13 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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Blotting, Western
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Bronchi / cytology
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Bronchi / immunology
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Bronchi / metabolism
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Cells, Cultured
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Chloride Channels / genetics*
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Chloride Channels / metabolism
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Enzyme Inhibitors / pharmacology
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Fluorescent Antibody Technique
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Gene Expression Regulation*
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Humans
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Interleukin-13 / pharmacology
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Janus Kinase 1
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Lung / cytology
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Lung / immunology
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Lung / metabolism
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Metaplasia / metabolism
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Metaplasia / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mucin 5AC
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Mucins / genetics*
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Mucins / metabolism
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Mucoproteins / genetics*
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Mucoproteins / metabolism
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Peptidoglycan / pharmacology
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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RNA, Messenger / metabolism
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Respiratory Mucosa / drug effects*
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Respiratory Mucosa / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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STAT6 Transcription Factor / genetics
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STAT6 Transcription Factor / physiology
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Trachea / cytology
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Trachea / immunology
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Trachea / metabolism
Substances
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CLCA1 protein, human
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Chloride Channels
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Clca3a1 protein, mouse
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Enzyme Inhibitors
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Interleukin-13
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MUC5AC protein, human
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Muc5ac protein, mouse
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Mucin 5AC
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Mucins
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Mucoproteins
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Peptidoglycan
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RNA, Messenger
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STAT6 Transcription Factor
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Protein-Tyrosine Kinases
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JAK1 protein, human
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Jak1 protein, mouse
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Janus Kinase 1