Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5504582 | Biochemical and Biophysical Research Communications | 2017 | 22 Pages |
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-1Â 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.
Keywords
EGFRTNFMUC1AECphorbol 12-myristate 13-acetateSTNFR1PAKIKKTLRqRT-PCRGAPDHNF-κBJnkc-Jun N-terminal kinaseERK1/2IκB kinasePMAMAPKMOIamino acidneutrophil elastaseinflammationinterleukinToll-like receptorairway epithelial cellPseudomonas aeruginosatumor necrosis factornuclear factor-κBMacrophageAlveolar macrophageQuantitative reverse transcriptase-polymerase chain reactionmitogen-activated protein kinasemultiplicity of infectionextracellular signal-regulated kinase 1/2glyceraldehyde 3-phosphate dehydrogenaseEpidermal growth factor receptor
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Authors
Kosuke Kato, Alec D. Hanss, Marina A. Zemskova, Nicole E. Morgan, Marianne Kim, Kenneth S. Knox, Yong Lin, Erik P. Lillehoj, Kwang Chul Kim,