Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells

Inoue, Daisuke; Yamaya, Mutsuo; Kubo, Hiroshi; Sasaki, Takuma; Hosoda, Masayoshi; Numasaki, Muneo; Tomioka, Y.; Yasuda, Hiroyasu; Sekizawa, Kiyohisa; Nishimura, Hidekazu; Sasaki, Hidetada

doi:10.1016/j.resp.2005.11.006

Cited by 72 publications

(67 citation statements)

References 28 publications

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“…A recent publication has described RV-14 mediated upregulation of MUC5AC via Src/MEK/NF-kB [12]. However, those authors overlooked the role of the EGFR and implied that NF-kB induced MUC5AC release directly.…”

Section: Discussionmentioning

confidence: 99%

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Rhinovirus induces MUC5AC in a human infection model and in vitro via NF- B and EGFR pathways

Hewson

Haas²,

Bartlett³

et al. 2010

European Respiratory Journal

106

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Rhinovirus (RV) infections are the major cause of asthma exacerbations, the major cause of morbidity and mortality in asthma. MUC5AC is the major mucin produced by bronchial epithelial cells. Whether RV infection upregulates MUC5AC in vivo is unknown and the molecular mechanisms involved are incompletely understood.We investigated RV induction of MUC5AC in vivo and in vitro to identify targets for development of new therapies for asthma exacerbations.RV infection increased MUC5AC release in normal and asthmatic volunteers experimentally infected with RV-16, and in asthmatic, but not normal, subjects, this was related to virus load. Bronchial epithelial cells were confirmed a source of MUC5AC in vivo. RV induction of MUC5AC in bronchial epithelial cells in vitro occurred via nuclear factor-kB-dependent induction of matrix metalloproteinase-mediated transforming growth factor-a release, thereby activating an epidermal growth factor receptor-dependent cascade culminating, via mitogen-activated protein kinase activation, in specificity protein-1 transactivation of the MUC5AC promoter.RV induction of MUC5AC may be an important mechanism in RV-induced asthma exacerbations in vivo. Revealing the complex serial signalling cascade involved identifies targets for development of pharmacologic intervention to treat mucus hypersecretion in RV-induced illness.

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Section: Discussionmentioning

confidence: 99%

“…One recent report investigated RV induction of MUC5AC in tracheal epithelial cells and reported nuclear factor (NF)-kB, mitogen-activated protein kinase kinase (MEK) and Src to be involved [12]. In contrast, most other reports investigating induction of MUC5AC by other stimuli in respiratory epithelial cells implicate EGFR and downstream pathways [13][14][15].…”

mentioning

confidence: 99%

Rhinovirus induces MUC5AC in a human infection model and in vitro via NF- B and EGFR pathways

Hewson

Haas²,

Bartlett³

et al. 2010

European Respiratory Journal

106

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“…In a study on primary human airway epithelial cultures, a panel of 20 cytokines (IL-1α, IL-1β, IL-2 to -18, and TNF-α) revealed that IL-6 and IL-17 were the only cytokines able to upregulate MUC5B and MUC5AC (97). Other agents that can upregulate MUC5B expression in airway epithelial cultures include RA, rhinovirus 14 infection, alpha defensins (human neutrophil peptides 1-3), and PMA (19,118,119). One report showed that IL-13 could upregulate MUC5B, although other studies have shown no effect (97,120).…”

Section: Upregulation Of Muc5b Expression In Airway Epithelial Cellsmentioning

confidence: 99%

Regulation of Airway Mucin Gene Expression

Thai

Loukoianov

Wachi

et al. 2008

Annu. Rev. Physiol.

192

223

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Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and airways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting airways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes.

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“…Specific pathogens, including Haemophilus influenzae, Staphylococcus pneumoniae, Pseudomonas aeruginosa, Mycoplasma pneumoniae, rhinovirus and respiratory syncytial virus, have been shown to increase mucus secretion [2][3][4][5][6]. Therefore, excessive mucus secretion may be a mechanism of infection-induced exacerbation of airway disease.…”

mentioning

confidence: 99%

Mycoplasma pneumoniae induces airway epithelial cell expression of MUC5AC in asthma

Kraft¹,

Adler²,

Ingram³

et al. 2008

European Respiratory Journal

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As excess mucin expression can contribute to the exacerbation of asthma, the present authors hypothesised that Mycoplasma pneumoniae significantly induces MUC5AC (the major airway mucin) expression in airway epithelial cells isolated directly from asthmatic subjects.A total of 11 subjects with asthma and six normal controls underwent bronchoscopy with airway brushing. Epithelial cells were cultured at an air-liquid interface and incubated with and without M. pneumoniae for 48 h, and in the presence and absence of nuclear factor (NF)-kB and a toll-like receptor (TLR)2 inhibitor. Quantitative PCR was performed for MUC5AC and TLR2 mRNA. MUC5AC protein and total protein were determined by ELISA.M. pneumoniae exposure significantly increased MUC5AC mRNA and protein expression after 48 h in epithelial cells isolated from asthmatic, but not from normal control subjects, at all concentrations as compared to unexposed cells. TLR2 mRNA expression was significantly increased in asthmatic epithelial cells at 4 h compared with unexposed cells. NF-kB and TLR2 inhibition reduced MUC5AC expression to the level of the unexposed control in both groups.Mycoplasma pneumoniae exposure significantly increased MUC5AC mRNA and protein expression preferentially in airway epithelial cells isolated from asthmatic subjects. The toll-like receptor 2 pathway may be involved in this process.

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Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells

Cited by 72 publications

References 28 publications

Rhinovirus induces MUC5AC in a human infection model and in vitro via NF- B and EGFR pathways

Rhinovirus induces MUC5AC in a human infection model and in vitro via NF- B and EGFR pathways

Regulation of Airway Mucin Gene Expression

Mycoplasma pneumoniae induces airway epithelial cell expression of MUC5AC in asthma

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