IL-13 Suppresses MUC5AC Gene Expression and Mucin Secretion in Nasal Epithelial Cells

Kim, Chang Hoon; Song, Kyoung Seob; Koo, Ja Seok; Kim, Hyun-Ung; Choi, Jae Young; Kim, Hyun Jun; Yoon, Joo‐Heon

doi:10.1080/000164802320396321

Cited by 25 publications

(18 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because IL-4/IL-13Rs are expressed on a wide range of cell types, subsequent studies have attempted to determine whether these cytokines act directly on epithelial cells to induce mucus metaplasia. Some studies showed IL-4 or IL-13 treatment of cultured airway epithelial cells increased mucus production and/or expression of transcripts encoding the major airway mucin Muc5ac (30 -34), but others did not (35)(36)(37)(38)(39)(40). IL-4 and IL-13 might also induce mucus production indirectly, via their ability to recruit and activate inflammatory cells such as neutrophils and eosinophils.…”

Section: Discussionmentioning

confidence: 99%

IL-4 Receptor Signaling in Clara Cells Is Required for Allergen-Induced Mucus Production

Kuperman

Huang²,

Nguyenvu³

et al. 2005

The Journal of Immunology

101

View full text Add to dashboard Cite

Excessive mucus production is an important pathological feature of asthma. The Th2 cytokines IL-4 and IL-13 have both been implicated in allergen-induced mucus production, inflammation, and airway hyperreactivity. Both of these cytokines use receptors that contain the IL-4Rα subunit, and these receptors are expressed on many cell types in the lung. It has been difficult to determine whether allergen-induced mucus production is strictly dependent on direct effects of IL-4 and IL-13 on epithelial cells or whether other independent mechanisms exist. To address this question, we used a cell type-specific inducible gene-targeting strategy to selectively disrupt the IL-4Rα gene in Clara cells, an airway epithelial cell population that gives rise to mucus-producing goblet cells. Clara cell-specific IL-4Rα-deficient mice and control mice developed similar elevations in serum IgE levels, airway inflammatory cell numbers, Th2 cytokine production, and airway reactivity following OVA sensitization and challenge. However, compared with control mice, Clara cell-specific IL-4Rα-deficient mice were nearly completely protected from allergen-induced mucus production. Because only IL-13 and IL-4 are thought to signal via IL-4Rα, we conclude that direct effects of IL-4 and/or IL-13 on Clara cells are required for allergen-induced mucus production in the airway epithelium.

show abstract

Section: Discussionmentioning

confidence: 99%

IL-4 Receptor Signaling in Clara Cells Is Required for Allergen-Induced Mucus Production

Kuperman

Huang²,

Nguyenvu³

et al. 2005

The Journal of Immunology

101

View full text Add to dashboard Cite

show abstract

“…Most of the studies were performed on cell lines or in animal models, and the data on primary epithelial cells are minimal. Recently, IL-13 has been shown to decrease MUC5AC gene expression and mucin secretion in cultured nasal epithelial cells (113). In another study, Chen et al (114) tested a panel of cytokines on primary human tracheal epithelial cells.…”

Section: Cytokine-induced Mucin Productionmentioning

confidence: 99%

Mucin Overproduction in Chronic Inflammatory Lung Disease

Hauber

Foley

Hamid

2006

Canadian Respiratory Journal

View full text Add to dashboard Cite

H-P Hauber, SC Foley, Q Hamid. Mucin overproduction in chronic inflammatory lung disease. Can Respir J 2006;13(6):327-335.Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed.Key Words: Bacteria; Cytokine; Lung; Mucin; Neutrophil elastase; Overproduction; Smoke La surproduction de mucine dans la pneumopathie inflammatoire chronique La surproduction de mucus et l'hypersécrétion sont courantes en présence d'une pneumopathie inflammatoire chronique. Les mucines sont des glycoprotéines gélifiantes qui peuvent être stimulées par divers médiateurs. La présente analyse traite des mécanismes de régulation positive des mucines sécrétées. Est également exposée l'induction des mucines par l'élastase des neutrophiles, les bactéries, les cytokines, les facteurs de croissance, la fumée et la défaillance du régulateur de conductance transmembraneuse de la fibrose kystique. M ucus is an important component of both the physiological and pathological processes in airways. It protects, moisturizes and lubricates mucosal surfaces, and traps bacteria and other inhaled irritants for removal by mucociliary clearance. However, excessive production of airway mucus is a feature of chronic inflammatory lung diseases such as bronchial asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and cystic fibrosis (CF). Mucus hypersecretion results from hyperplasia and metaplasia of mucous cells, which lead to greater numbers of these cells being found throughout the airways, including the distal airways, where they are normally absent (1). The presence of neutrophil elastase, certain bacterial pathogens and altered cytokine patterns all contribute to excess airway mucus production. This overproduction and hypersecretion of mucus, in turn, contributes to airway obstruction and impairment of mucociliary clearance.An understanding of the mechanisms that lead to mucus overproduction and secretion is therefore of great clinical interest. The present review provides insight into the mechanisms by which excessive mucus production is stimulated in chronic inflammatory lung disease, focusing mainly on enhanced gene expression and protein production of secretory mucins in the airways. MUCINSMucus is formed within the airways by a polymeric matrix of large, oligomeric, gel-forming glycoproteins, called mucins. These gel-forming mucins are primarily responsible for the rheological properties of airway mucus (2). However, in disease states such as CF and chronic bronchitis, polymeric DNA and filamentous actin, two products of leukocyte lysis, contribute greatly to, and are the principal determinants of, the viscoelastic properties of the purulent sputum...

show abstract

“…121 It however decreased MUC5AC expression in human nasal epithelial cells. 122 Other Th2 cytokines like IL-6, IL-9, IL-10 and IL-22 have also been shown to regulate mucin expression. IL-6 increased the expression of the gel-forming mucins, MUC2, MUC5AC, MUC5B and MUC6 and stimulated secretion in LS180 cells.…”

Section: Regulation Of Mucins By Cytokinesmentioning

confidence: 99%