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Novartis Foundation symposium2003; 248; 221-282;

The role of apoptotic regulators in metaplastic mucous cells.

Abstract: Exposure of airways to environmental toxins or allergens induces proliferation of epithelial cells. Depending on the type of exposure, existing and newly formed cells can differentiate into mucus-producing cells resulting in mucous cell metaplasia (MCM). During recovery, the epithelium reduces the number of epithelial cells to return to the original state. Understanding the mechanisms involved in this resolution could be useful in deleting mucous cells and, thereby, mucous secretions. We have found that metaplastic mucous cells induced by exposure to ozone, endotoxin, cigarette smoke or allergens in epithelia of various regions of the airways express Bcl-2, a regulator of apoptosis, and neutrophils appear to be involved in its expression. The percentage of Bcl-2-positive mucous cells is decreased prior to the resolution of MCM. Furthermore, targeted reduction of Bcl-2 expression causes a dose-dependent reduction of epithelial mucous cells, suggesting that Bcl-2 is involved in maintaining metaplastic mucous cells. Horses with recurrent airway obstruction show an increased percentage of Bcl-2-positive mucous cells compared to their normal counterparts. These studies suggest that down-regulation of Bcl-2 expression may be useful to reduce mucous secretions in diseased subjects. The role of Bax in the reduction of MCM during prolonged exposure to allergen is also discussed.
Publication Date: 2003-02-06 PubMed ID: 12568497
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.
  • Review

Summary

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This study attempts to understand how regulators of cell death, specifically Bcl-2, play a role in the overproduction of mucus in airway cells when exposed to allergens or toxins. It reveals that reducing Bcl-2 expression can reduce mucus production, which could be beneficial for conditions such as recurrent airway obstruction.

Research Methodology and Findings

  • The study observes that exposure to environmental elements such as toxins and allergens causes the airway epithelial cells to proliferate. Following the exposure, these cells can differentiate into mucus-producing cells leading to a condition called Mucous Cell Metaplasia (MCM).
  • The researchers noticed that during recovery, the number of epithelial cells is reduced to return to their original state. This process of resolution could be important for understanding how to remove excess mucus cells and, consequently, overproduction of mucus.
  • The researchers found that the excess mucus cells that are formed due to exposure to allergens, ozone, endotoxins, or cigarette smoke expressed the Bcl-2 protein, an apoptosis regulator. They also noticed that the expression of Bcl-2 seemed to involve the neutrophils.

The role of Bcl-2 and the possibility of reducing MCM

  • The study found a reduced percentage of Bcl-2 positive mucus cells before the resolution of MCM. This suggests that Bcl-2 is involved in maintaining the excess mucus cells.
  • When the expression of Bcl-2 was reduced, there was a decrease in mucus-producing cells in the airway lining in a dose-dependent manner. This finding supports the theory that Bcl-2 supports the maintenance of excess mucus cells.
  • Horses with recurrent airway obstruction showed an increase in the percentage of Bcl-2 positive mucus cells compared to healthy subjects. This hints towards the occurrence of Bcl-2 expression in diseases causing excess mucus production such as obstructive airway conditions.

Implications and Conclusion

  • Reducing Bcl-2 expression could potentially decrease mucus production, which could be very beneficial in treating diseased subjects with excessive mucus secretion.
  • The study also discusses the role of Bax, another proapoptotic protein, in reducing MCM during long-term exposure to allergens. This point suggests further possible ways of managing chronic mucus-related diseases.

Overall, the research suggests that understanding the role of apoptosis regulators like Bcl-2 could potentially assist in managing conditions related to excess production of mucus in the airways.

Cite This Article

APA
Tesfaigzi Y. (2003). The role of apoptotic regulators in metaplastic mucous cells. Novartis Found Symp, 248, 221-282.

Publication

ISSN: 1528-2511
NlmUniqueID: 9807767
Country: England
Language: English
Volume: 248
Pages: 221-282

Researcher Affiliations

Tesfaigzi, Yohannes
  • Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, USA.

MeSH Terms

  • Allergens / toxicity
  • Animals
  • Apoptosis / physiology
  • Bezafibrate / toxicity
  • Cell Division
  • Endotoxins / toxicity
  • Epithelial Cells / pathology
  • Exocrine Glands / pathology
  • Genes, bcl-2
  • Goblet Cells / metabolism
  • Goblet Cells / pathology
  • Inflammation / chemically induced
  • Inflammation Mediators / physiology
  • Lipopolysaccharides / toxicity
  • Metaplasia
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Ozone / toxicity
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Rats
  • Rats, Inbred BN
  • Smoke
  • bcl-2-Associated X Protein
  • bcl-X Protein

Grant Funding

  • ES09237 / NIEHS NIH HHS

Citations

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