Pseudomonas aeruginosa increases MUC1 expression in macrophages through the TLR4-p38 pathway

Kato, Kosuke; Hanss, Alec D.; Zemskova, Marina; Morgan, Nathaniel R.; Kim, Marianne; Knox, Kenneth S.; Lin, Yong; Lillehoj, Erik P.; Kim, Kwang Chul

doi:10.1016/j.bbrc.2017.08.056

Cited by 13 publications

(10 citation statements)

References 35 publications

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“…Given that P. aeruginosa binds to MUC1/Muc1 through its flagella [ 61 ], it is possible that this difference in phagocytosis may be related, in part, to the fact that S. pneumoniae is non-flagellated. We next investigated the mechanism through which P. aeruginosa regulates MUC1 expression by macrophages [ 87 ]. P. aeruginosa stimulation of human macrophages increased MUC1 expression both at the transcriptional and protein levels in a dose-dependent manner.…”

Section: Additional Role Of Airway Macrophages In the Anti-inflammentioning

confidence: 99%

MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function

Kato

Lillehoj

et al. 2017

JCM

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MUC1 is a membrane-bound mucin expressed on the apical surfaces of most mucosal epithelial cells. In normal lung epithelia, MUC1 is a binding site for Pseudomonas aeruginosa, an opportunistic human pathogen of great clinical importance. It has now been established that MUC1 also serves an anti-inflammatory role in the airways that is initiated late in the course of a bacterial infection and is mediated through inhibition of Toll-like receptor (TLR) signaling. MUC1 expression was initially shown to interfere with TLR5 signaling in response to P. aeruginosa flagellin, but has since been extended to other TLRs. These new findings point to an immunomodulatory role for MUC1 during P. aeruginosa lung infection, particularly during the resolution phase of inflammation. This review briefly summarizes the recent characterization of MUC1’s anti-inflammatory properties in both the respiratory tract and extrapulmonary tissues.

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Section: Additional Role Of Airway Macrophages In the Anti-inflammentioning

confidence: 99%

MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function

Kato

Lillehoj

et al. 2017

JCM

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“…Mechanistically, the results of the present study identified TLR4 as a direct target of miR-23a-5p in RASFs. TLR4, as a member of the TLR family, is widely distributed in various cells, such as T cells, B cells, lung macrophages, adipocytes and intestinal epithelial cells (52)(53)(54)(55). The extracellular domain of the TLR4 structure can combine with the myeloid differentiation-2/CD14 complex, identify pathogen-associated molecular patterns and eventually activate NF-κB signaling (56).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑23a‑5p regulates cell proliferation, migration and inflammation of TNF‑α‑stimulated human fibroblast‑like MH7A synoviocytes by targeting TLR4 in rheumatoid arthritis

Bao

2021

Exp Ther Med

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Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint inflammation. RA synovial fibroblasts (RASFs) constitute a major cell subset of the RA synovia. MicroRNAs (miRNAs/miRs) have been reported to serve a role in the activation and proliferation of RASFs. The present study aimed to investigate the effects and underlying mechanisms of miR-23a-5p on RA progression. Peripheral blood was collected from patients with RA (n=20) to analyze the expression levels of miR-23a-5p. The effects of miR-23a-5p on cell apoptosis, proliferation and migration in MH7A cells were determined in TNF-α-treated human fibroblast-like synoviocytes (MH7A cells) by flow cytometry, colony formation assay and Transwell assay, respectively. The cell cycle distribution was evaluated using flow cytometry. The binding relationship between miR-23a-5p and toll-like receptor (TLR) 4 was analyzed using a dual luciferase reporter gene assay. ELISA and reverse transcription-quantitative PCR assays were used to detect the levels of the inflammatory factors IL-6, IL-1β and IL-10. The expression levels of apoptosis- and migration-related proteins were analyzed using western blotting. The results of the present study revealed that the expression levels of miR-23a-5p were significantly downregulated in the plasma of patients with RA and in MH7A cells. In addition, the TNF-α-induced increase in the cell proliferative and migratory rates and the production of IL-6 and IL-1β were markedly inhibited following miR-23a-5p overexpression. The TNF-α-induced decreases in MH7A cell apoptosis were also reversed following miR-23a-5p overexpression. Additionally, transfection with miR-23a-5p mimics significantly inhibited the activation of the TLR4/NF-κB signaling pathway in TNF-α-treated MH7A cells by targeting TLR4. Notably, TLR4 overexpression weakened the effects of miR-23a-5p mimic on cell proliferation, apoptosis, migration, inflammation and the TLR4/NF-κB signaling pathway in TNF-α-induced MH7A cells. In conclusion, the findings of the present study indicated that the miR-23a-5p/TLR4/NF-κB axis may serve as a promising target for RA diagnosis and treatment.

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“…In primary human alveolar macrophages isolated from the BAL of healthy subjects and human monocytic cell line (THP-1 cells), P. aeruginosa infection significantly increased MUC1 expression compared to uninfected cells [57]. Macrophages recognize this bacterium through TLR4 and the stimulation of the THP-1 cells with P. aeruginosa increased MUC1 protein levels 5.4-fold, whereas pre-treatment with the viral inhibitory peptide of TLR4 significantly reduced P. aeruginosa-induced MUC1 RNA levels down to 1.3-fold [58]. Furthermore, P. aeruginosa infection of human NCI-H292 airway epithelial cells increased MUC5AC mRNA and protein [59].…”

Section: P Aeruginosamentioning

confidence: 98%

Role of the mucins in pathogenesis of COPD: implications for therapy

Bello

Ieni

Hansbro

et al. 2020

Expert Review of Respiratory Medicine

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Introduction: Evidence accumulated in the last decade has started to reveal the enormous complexity in the expression, interactions and functions of the large number of different mucins present in the different compartments of the human lower airways. This occurs both in normal subjects and in COPD patients in different clinical phases and stages of severity. Areas covered:We review the known physiological mechanisms that regulate mucin production in human lower airways of normal subjects, the changes in mucin synthesis/secretion in COPD patients and the clinical efficacy of drugs that modulate mucin synthesis/secretion. Expert opinion:It evident that the old simplistic concept that mucus hypersecretion in COPD patients is associated with negative clinical outcomes is valid and that the therapeutic potential of "mucolytic drugs" is under-appreciated due to the complexity of the associated molecular network(s). Likewise, our current knowledge of the effects of the drugs already available on the market that target mucin synthesis/secretion/structure in the lower airways is extremely limited and often indirect and more well-controlled clinical trials are needed in this area.

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Pseudomonas aeruginosa increases MUC1 expression in macrophages through the TLR4-p38 pathway

Cited by 13 publications

References 35 publications

MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function

MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function

MicroRNA‑23a‑5p regulates cell proliferation, migration and inflammation of TNF‑α‑stimulated human fibroblast‑like MH7A synoviocytes by targeting TLR4 in rheumatoid arthritis

Role of the mucins in pathogenesis of COPD: implications for therapy

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