Anti-inflammatory effect of MUC1 during respiratory syncytial virus infection of lung epithelial cells in vitro

Li, Yusheng; Dinwiddie, Darrell L.; Harrod, Kevin S.; Jiang, Yong; Kim, K. Chul

doi:10.1152/ajplung.00225.2009

Cited by 78 publications

(85 citation statements)

References 39 publications

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“…This results in inhibition of TLR signaling and a dampening of airway inflammation. This pathway has been elucidated in TLR5-dependent activation of primary epithelial cells in Pseudomonas aeruginosa infection, 14,15 but is also consistent with findings of negative regulation of other TLR molecules 12 and with the antiinflammatory effect of MUC1 during respiratory syncytial virus infection 13 and Haemophilus influenzae infection 44 of lung epithelial cells in vitro.…”

Section: Discussionsupporting

confidence: 84%

“…39 The towering structure of the MUC1 extracellular domain, estimated to be 200-500 nm in length when fully glycosylated, 21 plus expression of an abundance of terminally linked Neu5Ac is a likely first point of contact for HA binding by IAV that has penetrated the overlying gel mucus layer and gained access to the epithelial cell surface. Such chemoattraction and adherence to specific mucin carbohydrates have also been demonstrated for mouse adenovirus type I (MAVS-1) 40 and respiratory syncytial virus (RSV), 13 as well as bacteria including Campylobacter jejuni, 24 Helicobacter pylori 26 and Pseudomonas aeruginosa. 25 In this study we have been able to block IAV infection of MDCK cells with synthetic MUC1 glycopeptides expressing a2-6-linked Neu5Ac, with those having a longer peptide chain of 20 amino acids being much more efficient than glycopeptides of 11 amino acids in length.…”

Section: Discussionmentioning

confidence: 82%

“…In response to airway infection by Pseudomonas aeruginosa 12 and respiratory syncytial virus, 13 TLR activation in airway epithelial cells and macrophages induces the production of inflammatory mediators such as IL-8 (KC in the mouse) and TNFa to recruit effector cells. 14,15 In turn, MUC1 is upregulated and acts to suppress TLR signaling.…”

Section: Introductionmentioning

confidence: 99%

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The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

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Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency. Utilizing human lung epithelial cells, we found that IAV associates with the cs-mucin MUC1 but not MUC13 or MUC16. Overexpression of MUC1 by epithelial cells or the addition of sialylated synthetic MUC1 constructs, reduced IAV infection in vitro. In addition, Muc1 À / À mice infected with IAV exhibited enhanced morbidity and mortality, as well as greater inflammatory mediator responses compared to wild type mice. This study implicates the cs-mucin MUC1 as a critical and dynamic component of the innate host response that limits the severity of influenza and provides the foundation for exploration of MUC1 in resolving inflammatory disease.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 82%

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The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

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“…Muc1 overexpression in airway epithelial cells under pulmonary bacterial infection was considered as an immune response which in turn inhibits excessive inflammation and could be controlled by proinflammatory cytokine like TNF-α (9,19,20). AECOPD is mainly caused by bacterial infection in the airway and lung.…”

Section: Discussionmentioning

confidence: 99%

“…The CT domain of MUC1 mediates the cell signal transductions and cell adhesion. An indispensable antiinflammatory role of Muc1 has been found in the airway during Pseudomonas aeruginosa and respiratory syncytial virus infection (8,9). Muc1 levels in bronchoalveolar lavage (BAL) fluid were increased during the acute phase of lung inflammation and positively correlated with TNF-α level increase (8,10) and neutrophil elastase levels upregulation (11).…”

Section: Introductionmentioning

confidence: 99%

Sputum mucin 1 is increased during the acute phase of chronic obstructive pulmonary disease exacerbation

Zheng¹,

Qi²,

Xu³

et al. 2017

J. Thorac. Dis.

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Background: Mucin 1 (MUC1) is a membrane tethered protein on airway epithelial cells. This protein is upregulated and plays an important anti-inflammatory role during acute lung inflammation. However, the relationship between sputum MUC1 level and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is unknown. Methods:The levels of MUC1, IL-8, and TNF-α in induced sputum from 78 COPD patients were assessed by ELISA. The association between COPD exacerbation and MUC1 fragment levels was analyzed.An acute airway inflammation mouse model was established by intranasal LPS inhalation. The expression of Muc1 in lung and the levels of Muc1, TNF-α and KC in BAL fluid from mice were determined with western blotting and ELISA, respectively.Results: Higher levels of MUC1 membrane-tethered (CT) and extracellular (EC) fragments, cytokines TNF-α and IL-8, more leucocyte and neutrophil counts were found in sputum from COPD patients in acute than in remission phase. Linear regression analysis confirmed that the level of sputum MUC1 CT fragment is positively correlated with sputum neutrophil number and patients' age; whereas the sputum EC fragment level is correlated inversely with FEV1/FVC value and positively with patients' age. Inhalation of lipopolysaccharide (LPS) induced acute lung inflammation in mice which exhibited increased levels of Muc1 CT fragment in lung and only Muc1 EC fragment increase in BAL fluid.Conclusions: Unlike pure bacterial induced lung inflammation, both sputum MUC1 CT and EC fragments are increased during acute exacerbation of COPD. The clinical benefits from measuring the changes of various sputum MUC1 fragments in AECOPD need to be elucidated in future studies.

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Assessment of toxicological effects of favipiravir (T‐705) on the lung tissue of rats: An experimental study

Erbaş,

Celep,

Tekiner

et al. 2023

J Biochem & Molecular Tox

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This study aimed to present new data on the side effects of favipiravir on healthy lung tissue and the respiratory system. In the study, two different durations (5 and 10 days) were preferred to determine the effect of favipiravir treatment due to clinical improvement rates of approximately 5 and 10 days during the use of favipiravir in COVID‐19 patients. In addition, after 10 days of favipiravir treatment, animals were kept for 5 days without any treatment to determine the regeneration of lung tissues. Favipiravir was administered to rats by oral gavage at a daily dose of 200 mg/kg for 5 and 10 days, as in previous studies. At the end of the experiment, the histopathological and biochemical effects of favipiravir in the lung tissue were investigated. The data obtained from the study showed that favipiravir increased oxidative stress parameters, expression of apoptotic markers, and pro‐inflammatory markers in lung tissue. Since malondialdehydes is an oxidant parameter, it increased in favipiravir‐administered groups; It was determined that the antioxidant parameters glutathione, superoxide dismutase, glutathione peroxidase, and catalase decreased. Other markers used in the analysis are Bcl‐2, Bax, NF‐κB, interleukin (IL)‐6, Muc1, iNOS, P2X7R, IL‐6 and caspase‐3. The levels of Bax, caspase‐3, NF‐κB, IL‐6, Muc1, and P2X7R were increased in the Fav‐treated groups compared with the control. However, the levels of Bcl‐2 decreased in the Fav‐treated groups. The present study proves that favipiravir, widely used today, causes side effects in lung tissue.

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Anti-inflammatory effect of MUC1 during respiratory syncytial virus infection of lung epithelial cells in vitro

Cited by 78 publications

References 39 publications

The cell surface mucin MUC1 limits the severity of influenza A virus infection

The cell surface mucin MUC1 limits the severity of influenza A virus infection

Sputum mucin 1 is increased during the acute phase of chronic obstructive pulmonary disease exacerbation

Assessment of toxicological effects of favipiravir (T‐705) on the lung tissue of rats: An experimental study

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