title: IL-13 Inhibits Multicilin Expression and Ciliogenesis via Janus Kinase/Signal Transducer and Activator of Transcription Independently of Notch Cleavage.
abstract: Loss of ciliated cells and increases in goblet cells are seen in respiratory diseases such as asthma. These changes result in part from reduced differentiation of basal progenitor cells to ciliated cells during injury and repair. The T helper 2 cytokine, IL-13, has been shown to inhibit ciliated cell differentiation, but the mechanism is not clearly understood. We recently showed that Notch signaling inhibits ciliated cell differentiation in submerged culture by repressing multicilin and forkhead box J1 (FOXJ1) expression, genes required for ciliogenesis. Using a novel method to study ciliated cell differentiation, we investigated the relationship between IL-13 and Notch signaling pathways. We found that IL-13 inhibits ciliated cell differentiation by repressing multicilin and FOXJ1 expression but does so independent of Notch signaling. In addition, we show that pharmacological inhibition of Janus kinase/signal transducer and activator of transcription, but not mitogen activated protein kinase kinase, signaling rescues multicilin and FOXJ1 expression and ciliated cell differentiation in the presence of IL-13. These findings indicate that regulation of multicilin expression by two distinct signaling pathways affects ciliated cell differentiation. In addition, the requirement for Janus kinase activation in IL-13-induced inhibition of ciliogenesis provides a potential therapeutic target for the treatment of respiratory disease.
authors.affiliation: Department of Cell Biology, University of Miami School of Medicine, Miami, Florida.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Gerovac
authors.affiliation: Department of Cell Biology, University of Miami School of Medicine, Miami, Florida.
authors.forename: Nevis L
authors.initials: NL
authors.lastname: Fregien
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002923:Cilia; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D053612:Janus Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D018797:Cell Cycle Proteins; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D018793:Interleukin-13; C560898:MCIDAS protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D050791:STAT Transcription Factors; D014157:Transcription Factors; D053612:Janus Kinases
keywords: IL-13; Janus kinase/signal transducer and activator of transcription; Notch; multicilin; multiciliogenesis