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

Kato, Kosuke; Lillehoj, Erik P.; Lu, Wenju; Kim, Kwang Chul

doi:10.3390/jcm6120110

Cited by 56 publications

(61 citation statements)

References 117 publications

(159 reference statements)

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“…An important function of MUC1 in the lung is to protect underlying cells and facilitate clearance of invading microbes such as Pneumocystis (Rose & Voynow, ). Intriguingly, MUC1 can mediate adherence of P. aeruginosa to lung epithelial cells, and appears to facilitate infection and decrease inflammation (Kato et al, ; Kato et al, ). If it were operating in a similar manner in Pneumocystis infection, it is possible that MUC1 expression in the alveoli may facilitate infection with Pneumocystis by allowing attachment of air‐borne cysts that can subsequently release the replicating trophic forms.…”

Section: Discussionmentioning

confidence: 99%

“…MUC1 can mediate binding of microorganisms such as Pseudomonas aeruginosa to lung epithelial cells (Kato, Lillehoj, Kai, & Kim, ); such binding can dampen inflammatory responses (Kato, Lillehoj, Lu, & Kim, ). It is unknown if MUC1 plays a role in Pneumocystis invasion and pathogenesis, although serum MUC1 levels have been evaluated for the serodiagnosis of PCP (Esteves et al, ), and higher levels of MUC1 (KL‐6) were associated with greater mortality in a retrospective study of intensive care patients with PCP (Kotani et al, ).…”

Section: Introductionmentioning

confidence: 99%

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MUC1 mediatesPneumocystis murinabinding to airway epithelial cells

Liu

Davis

et al. 2020

Cellular Microbiology

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Previous studies have shown that Pneumocystis binds to pneumocytes, but the proteins responsible for binding have not been well defined. Mucins are the major glycoproteins present in mucus, which serves as the first line of defence during airway infection.MUC1 is the best characterised membrane-tethered mucin and is expressed on the surface of most airway epithelial cells. Although by electron microscopy Pneumocystis primarily binds to type I pneumocytes, it can also bind to type II pneumocytes. We hypothesized that Pneumocystis organisms can bind to MUC1 expressed by type II pneumocytes. Overexpression of MUC1 in human embryonic kidney HEK293 cells increased Pneumocystis binding, while knockdown of MUC1 expression by siRNA in A549 cells, a human adenocarcinoma-derived alveolar type II epithelial cell line, decreased Pneumocystis binding. Immunofluorescence labelling indicated that MUC1and Pneumocystis were co-localised in infected mouse lung tissue. Incubation of A549 cells with Pneumocystis led to phosphorylation of ERK1/2 that increased with knockdown of MUC1 expression by siRNA. Pneumocystis caused increased IL-6 and IL-8 secretion by A549 cells, and knockdown of MUC1 further increased their secretion in A549 cells. Taken together, these results suggest that binding of Pneumocystis to MUC1 expressed by airway epithelial cells may facilitate establishment of productive infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MUC1 mediatesPneumocystis murinabinding to airway epithelial cells

Liu

Davis

et al. 2020

Cellular Microbiology

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“…1, IL-1β, IL-6, and Muc1 gene expression was upregulated in the B. bronchiseptica induction group, whereas the genes were decreased in a dose-dependent manner when the Bor-BRP-1 phage was applied for 24 h prior to B. bronchiseptica infection. This is interesting because IL-1β and IL-6 are important mediators of inflammation even though Muc1 is a membrane-bound mucin that serves an anti-inflammatory role (Kato et al 2017). It is implied that Bor-BRP-1 could suppress release of proinflammatory cytokines as well as anti-inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

“…1a, b). Muc1 is known as an anti-inflammatory mucin (Kato et al 2017). Since the airway inflammatory environment was decreased by Bor-BRP-1, Muc1 gene expression decreased proportional to the status of anti-inflammation.…”

Section: Bor-brp-1 Significantly Inhibited B Bronchiseptica-induced mentioning

confidence: 99%

Specific bacteriophage of Bordetella bronchiseptica regulates B. bronchiseptica-induced microRNA expression profiles to decrease inflammation in swine nasal turbinate cells

Park

Son

et al. 2020

Genes Genom

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Background Respiratory diseases in pigs are the main health concerns for swine producers. Similar to the diseases in human and other animals, respiratory diseases are primary related to morbidity and are the result of infection with bacteria, viruses, or both. B. bronchiseptica causes serious respiratory diseases in the swine airway track. However, the B. bronchisepticaspecific bacteriophage has diverse advantages such as decreasing antibiotic overuse and possible therapeutic potential against bacteria.Objective The objects of this study were to investigate the therapeutic effect of specific B. bronchiseptica bacteriophages and to identify genes related to bacteriophage signaling utilizing RNA microarrays in swine nasal turbinate cells. Methods Bor-BRP-1 phages were applied 24 h prior to B.bronchiseptica infection (1 × 10 7 cfu/ml) at several concentrations of bacterial infection. Cells were incubated to detect cytokines and 24 h to detect mucin production. And real-time quantitative PCR was performed to examine related genes expression. To determine the change of total gene expression based on B.bronchiseptica and Bor-BRP-1 treatment, we performed RNA sequencing experiments. Results The results showed that B. bronchiseptica induced increased expression of several inflammatory genes such as IL-1β, IL-6, and Muc1 in a dose-dependent manner. However, Bor-BRP-1 induced reduction of gene expression compared to the B. bronchiseptica induction group. In addition, microarrays detected Bor-BRP-1-altered inflammatory gene expression against B. bronchiseptica, reducing B. bronchiseptica-induced airway inflammation in swine epithelial cells. Conclusion These results suggest that the specific bacteriophage has a therapeutic potential to defend against B. bronchiseptica infection by altering inflammatory gene expression profiles. Song declare that we have no conflict of interest.Ethical approval This article does not contain any studies with human subjects or animals performed by any of the authors.

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“…Tumor-associated MUC1 (tMUC1) is overexpressed and aberrantly glycosylated in more than 80% of PDA cases [17][18][19][20][21]. In 4 normal environments, MUC1 is expressed on the apical surface of ductal cells to provide a protective barrier [22]. However, upon tumorigenesis MUC1 expression is no longer restricted to the apical surface.…”

Section: Introductionmentioning

confidence: 99%

Tumor -Associated MUC1 Regulates TGF-β Signaling and Function in Pancreatic Ductal Adenocarcinoma

Grover

Nath²,

Bose

et al. 2020

Preprint

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Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human cancers.Transforming Growth Factor Beta (TGF-β) is a cytokine that switches from a tumorsuppressor to a tumor promoter throughout tumor development, by a yet unknown mechanism. Tumor associated MUC1 (tMUC1) is aberrantly glycosylated and overexpressed in >80% of PDAs and is associated with poor prognosis. The cytoplasmic tail of MUC1 (MUC1-CT) interacts with other oncogenic proteins promoting tumor progression and metastasis. We hypothesize that tMUC1 levels regulate TGF-β functions in PDA in vitro and in vivo. We report that high-tMUC1 expression positively correlates to TGF-βRII and negatively to TGF-βRI receptors. In response to TGF-β1, high tMUC1 expressing PDA cells undergo c-Src phosphorylation, and activation of the Erk/MAPK 2 pathway; while low tMUC1 expressing cells activate the Smad2/3 pathway, enhancing cell death. Correspondingly, mice bearing tMUC1-high tumors responded to TGF-β1 neutralizing antibody in vivo showing significantly retarded tumor growth. Analysis of clinical data from TCGA revealed significant alterations in gene-gene correlations in the TGF-β pathway in tMUC1 high versus tMUC1 low samples. This study deepens our understanding of tMUC1-regulated TGF-β's paradoxical function in PDA and establishes tMUC1 as a potential biomarker to predict response to TGF-β-targeted therapies.

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

Cited by 56 publications

References 117 publications

MUC1 mediatesPneumocystis murinabinding to airway epithelial cells

MUC1 mediatesPneumocystis murinabinding to airway epithelial cells

Specific bacteriophage of Bordetella bronchiseptica regulates B. bronchiseptica-induced microRNA expression profiles to decrease inflammation in swine nasal turbinate cells

Tumor -Associated MUC1 Regulates TGF-β Signaling and Function in Pancreatic Ductal Adenocarcinoma

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