ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Membrane-tethered MUC1 mucin is phosphorylated by epidermal growth factor receptor in airway epithelial cells and associates with TLR5 to inhibit recruitment of MyD88.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond.Frontiers in immunology · 2022Pooled it
- MUC1 in the upper-lower airway inflammatory continuum: an endotype-centered perspective.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Transmembrane mucins in lung adenocarcinoma: understanding of current molecular mechanisms and clinical applications.Cell death discovery · 2025Review
- Article
- MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-κB pathway.Respiratory research · 2023Article
- Roles unveiled for membrane-associated mucins at the ocular surface using a Muc4 knockout mouse model.Scientific reports · 2023Article
- Innate immune responses in pneumonia.Pneumonia (Nathan Qld.) · 2023Review
- Article
- Membrane-associated mucins of the human ocular surface in health and disease.The ocular surface · 2021Review
- The role of mucin 1 in respiratory diseases.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Defensive Properties of Mucin Glycoproteins during Respiratory Infections-Relevance for SARS-CoV-2.mBio · 2020Review
- The interaction ofMicrobiology (Reading, England) · 2020Article
- MUC1 contributes to goblet cell metaplasia and MUC5AC expression in response to cigarette smoke in vivo.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Membrane-associated mucins of the ocular surface: New genes, new protein functions and new biological roles in human and mouse.Progress in retinal and eye research · 2020Review
- The human transmembrane mucin MUC17 responds to TNFα by increased presentation at the plasma membrane.The Biochemical journal · 2019Article
- The Role of the Cell Surface Mucin MUC1 as a Barrier to Infection and Regulator of Inflammation.Frontiers in cellular and infection microbiology · 2019Review
- MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease.Respiratory research · 2018Article
- MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function.Journal of clinical medicine · 2017Review
- The cell surface mucin MUC1 limits the severity of influenza A virus infection.Mucosal immunology · 2017Article
- Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer.Journal of innate immunity · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
MUC1 is a membrane-tethered mucin glycoprotein expressed on the apical surface of mucosal epithelial cells. Previous in vivo and in vitro studies established that MUC1 counterregulates airway inflammation by suppressing TLR signaling. In this article, we elucidate the mechanism by which MUC1 inhibits TLR5 signaling. Overexpression of MUC1 in HEK293 cells dramatically reduced Pseudomonas aeruginosa-stimulated IL-8 expression and decreased the activation of NF-κB and MAPK compared with cells not expressing MUC1. However, overexpression of MUC1 in HEK293 cells did not affect NF-κB or MAPK activation in response to TNF-α. Overexpression of MyD88 abrogated the ability of MUC1 to inhibit NF-κB activation, and MUC1 overexpression inhibited flagellin-induced association of TLR5/MyD88 compared with controls. The MUC1 cytoplasmic tail associated with TLR5 in all cells tested, including HEK293T cells, human lung adenocarcinoma cell line A549 cells, and human and mouse primary airway epithelial cells. Activation of epidermal growth factor receptor tyrosine kinase with TGF-α induced phosphorylation of the MUC1 cytoplasmic tail at the Y46EKV sequence and increased association of MUC1/TLR5. Finally, in vivo experiments demonstrated increased immunofluorescence colocalization of Muc1/TLR5 and Muc1/phosphotyrosine staining patterns in mouse airway epithelium and increased Muc1 tyrosine phosphorylation in mouse lung homogenates following P. aeruginosa infection. In conclusion, epidermal growth factor receptor tyrosine phosphorylates MUC1, leading to an increase in its association with TLR5, thereby competitively and reversibly inhibiting recruitment of MyD88 to TLR5 and downstream signaling events. This unique ability of MUC1 to control TLR5 signaling suggests its potential role in the pathogenesis of chronic inflammatory lung diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.