PAF mediates cigarette smoke-induced goblet cell metaplasia in guinea pig airways

Komori, Motofumi; Inoue, Hiromasa; Matsumoto, Koichiro; Kojima, Hiroshi; Fukuyama, Satoru; Aizawa, Hisamichi; Hara, Nobuyuki

doi:10.1152/ajplung.2001.280.3.l436

Cited by 17 publications

(12 citation statements)

References 36 publications

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“…In mice, these effects are dependent on macrophage, rather than neutrophil, inflammation (28). One mediator that regulates the secretory metaplastic response to cigarette smoke in guinea pig airways is platelet activating factor (137).…”

Section: Mucin Regulation By Inflammatory Mediators In Vitro and In Vmentioning

confidence: 99%

Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease

Rose

Voynow²

2006

Physiological Reviews

945

892

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This review focuses on the role and regulation of mucin glycoproteins (mucins) in airway health and disease. Mucins are highly glycosylated macromolecules (≥50% carbohydrate, wt/wt). MUC protein backbones are characterized by numerous tandem repeats that contain proline and are high in serine and/or threonine residues, the sites of O-glycosylation. Secretory and membrane-tethered mucins contribute to mucociliary defense, an innate immune defense system that protects the airways against pathogens and environmental toxins. Inflammatory/immune response mediators and the overproduction of mucus characterize chronic airway diseases: asthma, chronic obstructive pulmonary diseases (COPD), or cystic fibrosis (CF). Specific inflammatory/immune response mediators can activate mucin gene regulation and airway remodeling, including goblet cell hyperplasia (GCH). These processes sustain airway mucin overproduction and contribute to airway obstruction by mucus and therefore to the high morbidity and mortality associated with these diseases. Importantly, mucin overproduction and GCH, although linked, are not synonymous and may follow from different signaling and gene regulatory pathways. In section i, structure, expression, and localization of the 18 human MUC genes and MUC gene products having tandem repeat domains and the specificity and application of MUC-specific antibodies that identify mucin gene products in airway tissues, cells, and secretions are overviewed. Mucin overproduction in chronic airway diseases and secretory cell metaplasia in animal model systems are reviewed in section ii and addressed in disease-specific subsections on asthma, COPD, and CF. Information on regulation of mucin genes by inflammatory/immune response mediators is summarized in section iii. In section iv, deficiencies in understanding the functional roles of mucins at the molecular level are identified as areas for further investigations that will impact on airway health and disease. The underlying premise is that understanding the pathways and processes that lead to mucus overproduction in specific airway diseases will allow circumvention or amelioration of these processes.

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Section: Mucin Regulation By Inflammatory Mediators In Vitro and In Vmentioning

confidence: 99%

Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease

Rose

Voynow²

2006

Physiological Reviews

945

892

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“…Smokers with COPD also show goblet cell metaplasia and submucosal gland hypertrophy (Innes et al, 2006). Increased EGF receptor expression and activation and increased expression of platelet activating factor caused by cigarette smoke are thought to play a role in development of goblet cell metaplasia (Curran and Cohn, 2010;Komori et al, 2001;O'Donnell et al, 2004). Cigarette smoke decreases water and ion transport by inhibiting apical chloride channel and basolaterally located potassium channel in primary human and mouse airway epithelial cells Savitski et al, 2009).…”

Section: Mucociliary Clearancementioning

confidence: 99%

Innate Immunity of Airway Epithelium and COPD

Ganesan¹,

Sajjan²

2012

Emphysema

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“…In contrast, cigarette smoke exposure has little effect in the mouse (Bartalesi et al, 2005) with only a few secretory cells appearing in the small airways. In the larger airways cigarette smoke-exposed rats (Rogers et al, 1986) and guinea pigs (Komori et al, 2001) exhibit significant goblet cell metaplasia which can be attenuated with treatment with anti-inflammatory agents and antioxidants.…”

Section: Chronic Bronchitismentioning

confidence: 99%