Pseudomonas aeruginosa increases MUC1 expression in macrophages through the TLR4-p38 pathway
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Author
Kato, KosukeHanss, Alec D
Zemskova, Marina A
Morgan, Nicole E
Kim, Marianne
Knox, Kenneth S
Lin, Yong
Lillehoj, Erik P
Kim, Kwang Chul
Affiliation
Univ Arizona, Coll Med, Dept MedIssue Date
2017-10-14
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ACADEMIC PRESS INC ELSEVIER SCIENCECitation
Kato, K., Hanss, A. D., Zemskova, M. A., Morgan, N. E., Kim, M., Knox, K. S., ... & Kim, K. C. (2017). Pseudomonas aeruginosa increases MUC1 expression in macrophages through the TLR4-p38 pathway. Biochemical and biophysical research communications, 492(2), 231-235.Rights
© 2017 Elsevier Inc. All rights reserved.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Alveolar macrophages (AMs) play a critical role in the clearance of Pseudomonas aeruginosa (Pa) from the airways. However, hyper-activation of macrophages can impair bacterial clearance and contribute to morbidity and mortality. MUC1 mucin is a membrane-tethered, high molecular mass glycoprotein expressed on the apical surface of mucosal epithelial cells and some hematopoietic cells, including macrophages, where it counter-regulates inflammation. We recently reported that Pa up-regulates the expression of MUC1 in primary human AMs and THP-1 macrophages, and that increased MUC1 expression in these cells prevents hyper-activation of macrophages that appears to be important for host defense against severe pathology of Pa lung infection. The aims of this study were to elucidate the mechanism by which Pa increases MUC1 expression in macrophages. The results showed that: (a) Pa stimulation of THP-1 macrophages increased MUC1 expression both at transcriptional and protein levels in a dose-dependent manner; (b) Both Pa- and LPS-induced MUC1 expression in THP-1 cells were significantly diminished by an inhibitory peptide of TLR4; and (c) LPS-stimulated MUC1 expression was diminished at both the mRNA and protein levels by an inhibitor of the p38 mitogen-activated protein kinase, but not by inhibitors of ERK1/2, JNK, or IKK. We conclude that Pa-stimulated MUC1 expression in THP-1 macrophages is regulated mainly through the TLR4-p38 signaling pathway. (C) 2017 Elsevier Inc. All rights reserved.Note
12 month embargo; published online: 16 August 2017ISSN
1090-2104PubMed ID
28822766Version
Final accepted manuscriptae974a485f413a2113503eed53cd6c53
10.1016/j.bbrc.2017.08.056
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