Suppression of MUC5AC expression in human bronchial epithelial cells by interferon-γ

Oyanagi, Takahito; Takizawa, Takumi; Aizawa, Akira; Orosoo, Solongo; Yagi, Hisako; Nishida, Yutaka; Koyama, Harumi; Saitoh, Akihiko; Arakawa, Hirokazu

doi:10.1016/j.alit.2016.05.005

Cited by 13 publications

(13 citation statements)

References 29 publications

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“…IFN-γ has pleiotropic effects on the epithelial cells of the respiratory tract. This cytokine has been shown to reduce MUC5AC expression, which may lead to a decrease in the barrier property of the respiratory mucus (48). In the meantime, IFN-γ induces the expression of CEACAM receptors (49) that are the receptors for the meningococcal adhesin Opa, known to be involved in the internalization of bacteria.…”

Section: Discussionmentioning

confidence: 99%

Airway Mucus Restricts Neisseria meningitidis Away from Nasopharyngeal Epithelial Cells and Protects the Mucosa from Inflammation

Audry

Robbe-Masselot

Barnier

et al. 2019

mSphere

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N. meningitidis is transmitted from person to person by aerosol droplets produced by breathing, talking, or coughing or by direct contact with a contaminated fluid. The natural reservoir of N. meningitidis is the human nasopharynx mucosa, located at the back of the nose and above the oropharynx. The means by which meningococci cross the nasopharyngeal wall is still under debate, due to the lack of a convenient and relevant model mimicking the nasopharyngeal niche. Here, we took advantage of Calu-3 cells grown in air interface culture to study how meningococci colonize the nasopharyngeal niche. We report that the airway mucus is both a niche for meningococcal growth and a protective barrier against N. meningitidis infection. As such, N. meningitidis behaves like commensal bacteria and is unlikely to induce infection without an external trigger.

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Section: Discussionmentioning

confidence: 99%

Airway Mucus Restricts Neisseria meningitidis Away from Nasopharyngeal Epithelial Cells and Protects the Mucosa from Inflammation

Audry

Robbe-Masselot

Barnier

et al. 2019

mSphere

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“…IFNγ and IL-12 are known to be associated with macrophage and dendritic cells response, although there are evidences that epithelial cells produce these cytokines after infection with microbes 46,47 IFNγ has pleiotropic effects on the epithelial cells of the respiratory tract. This cytokine has been shown to reduce MUC5AC expression, which may lead to a decrease in the barrier property of the respiratory mucus 48 .…”

Section: Discussionmentioning

confidence: 99%

Air-interfaced colonization model suggests a commensal-like interaction ofNeisseria meningitidiswith the epithelium, which benefit from colonization byStreptococcus mitis

Audry

Robbe-Masselot

Barnier

et al. 2019

Preprint

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Neisseria meningitidis is an inhabitant of the nasopharynx, from which it is transmitted from person to person or disseminates in the blood and becomes a harmful pathogen. In this work, we addressed the colonization of the nasopharyngeal niche by focusing on the interplay between meningococci and the mucus that lines the mucosa of the host. Using Calu-3 cells grown in air-interfaced culture, we studied the meningococcal colonization of the mucus and the host response. Our results suggested that N. meningitidis behaved like commensal bacteria in mucus, without interacting with human cells or actively transmigrating through the cell layer. As such, meningococci did not trigger a strong innate immune response from the Calu-3 cells. Finally, we have shown that this model is suitable for studying interaction of N. meningitidis with other bacteria living in the nasopharynx, and that Streptococcus mitis but not Moraxella catarrhalis can promote meningococcal growth in this model.

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“…Transcriptional regulation of MUC5AC expression and MUC5AC protein expression in the airways has been directly linked to EGFR-mediated activation of Sp-1. 58,60,62,64 Although limited, the evidence appears to be highly reproducible across several studies in human airway epithelial cells, thereby supporting moderate biological plausibility of KERs KE1/KE5: EGFR activation indirectly leading to Sp-1 activation and KE5/KE6: Sp-1 activation directly leading to increased mucin production.…”

Section: Summary Of Kes and Mechanismsmentioning

confidence: 73%

“…Activation of EGFR by oxidative stress was shown to correlate with increased mucin mRNA and protein expression, involving classical EGFR signal transduction through the MAPK cascade to activate the Sp-1 (KE5: Sp-1 Activa-tion) or, at least in mice, hypoxia-inducible factor-1 alpha (HIF-1a) transcription factors that govern MUC5AC gene expression. [58][59][60][61][62][63][64] In addition, activation of EGFR can also downregulate FOXA2, a known transcriptional repressor of mucin genes, although the underlying mechanism is currently unknown. 65,66 Alternatively, mucin production could be stimulated by other, concomitant oxidative stressinduced, but EGFR-independent, processes known to contribute to GCH/GCM and increased expression of mucins.…”

Section: Summary Of Kes and Mechanismsmentioning

confidence: 99%

The Adverse Outcome Pathway for Oxidative Stress-Mediated EGFR Activation Leading to Decreased Lung Function

LuettichKarsta

TalikkaMarja

LoweFrazer

et al. 2017

Applied In Vitro Toxicology

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The Adverse Outcome Pathway (AOP) framework provides a means to outline a knowledge-driven sequence of events from exposure to adverse outcome. As a concept, AOPs have been readily accepted by the toxicology community as a means to organize available mechanistic information linking exposures to toxic effects in a standardized way encompassing all organizational levels of a given biological system. However, there is also an inherent benefit in applying AOPs to health outcomes that are not necessarily linked to standard toxicological end points, for example, in the context of predicting disease risk or in drug development. In this study, we propose an AOP for decreased lung function that originates in oxidative stress-mediated epidermal growth factor receptor activation in the airway epithelium. This article provides an overview of the supporting evidence for key events (KEs) on the molecular, cellular, tissue/organ, and organism level and how they relate to each other through key event relationships (KERs). The essentiality of the identified KEs, as well as the biological plausibility of the KERs, is also assessed. Moreover, the envisioned application of the proposed AOP is discussed, highlighting the utility of the AOP framework for developing preclinical tests that could prove useful in public health risk assessment for long-term e-cigarette use.

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Suppression of MUC5AC expression in human bronchial epithelial cells by interferon-γ

Abstract: These results suggest that IFN-γ represses MUC5AC expression, disturbing binding of Sp1 to its target sequences.

Cited by 13 publications

References 29 publications

Airway Mucus Restricts Neisseria meningitidis Away from Nasopharyngeal Epithelial Cells and Protects the Mucosa from Inflammation

Airway Mucus Restricts Neisseria meningitidis Away from Nasopharyngeal Epithelial Cells and Protects the Mucosa from Inflammation

Air-interfaced colonization model suggests a commensal-like interaction ofNeisseria meningitidiswith the epithelium, which benefit from colonization byStreptococcus mitis

The Adverse Outcome Pathway for Oxidative Stress-Mediated EGFR Activation Leading to Decreased Lung Function

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