New insights into airway mucous cell differentiation

Reen Wu, Richart Harper, Cheng Yuan Kao, Philip Thai, Daphne Wu, Yin Chen, Mary M.J. Chang

Research output: Contribution to journalReview article

4 Scopus citations

Abstract

Chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis are characterized by persistent airway inflammation and the overproduction of mucus in airways. So-called "goblet (mucous) cell metaplasia/hyperplasia" is the pathologic feature in these diseased airways, in which the normal mucociliary epithelium is replaced by goblet/mucous cells. The nature of the goblet/mucous cell population which arises in these diseased airways is unknown. Our recent studies have shown that trans-differentiation of surface epithelial cells occurs so that they express the submucosal gland-type mucin gene, MUC5B , in addition to a general elevation of all mucin gene products in surface epithelial cells as well as in the submucosal area. In contrast to MUC5B , the surface type of mucin gene, MUC5AC , is restrictedly expressed in the surface epithelium. Using a panel of cytokines - interleukin (IL)-1a, -1ß, -2, -3, -4, -5, -6, -7, -8, -9, -10, -11, -12, -13, -15, -16, -17, -18, and -19, and tumor necrosis factor-a - we have found to our surprise that only IL-6 and -7 can directly stimulate both MUC5AC and MUC5B expression in well-differentiated and polarized primary human airway epithelial cell cultures. Other cytokines, such as the Th2 type IL-4, -5, -9, and -13, cannot. Inhibitor and signaling transduction studies revealed the presence of an IL-6 paracrine/autocrine loop and the dependence on extracellular signal-regulated kinase signaling activation in IL-17-stimulated mucin gene expression. Further studies are needed to connect cytokine-based mucin gene expression and the trans-differentiation phenomenon in airway diseases.

Original languageEnglish (US)
Pages (from-to)30-36
Number of pages7
JournalJournal of Organ Dysfunction
Volume2
Issue number1
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Keywords

  • Airway epithelial cells
  • Cytokines
  • Lung diseases
  • Mucin
  • Mucous cell differentiation

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Critical Care
  • Critical Care and Intensive Care Medicine

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  • Cite this

    Wu, R., Harper, R., Kao, C. Y., Thai, P., Wu, D., Chen, Y., & Chang, M. M. J. (2006). New insights into airway mucous cell differentiation. Journal of Organ Dysfunction, 2(1), 30-36. https://doi.org/10.1080/17471060600580672