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New insights into airway mucous cell differentiation

Journal of Organ Dysfunction, ISSN: 1747-1060, Vol: 2, Issue: 1, Page: 30-36
2006
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Review Description

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. © 2006 Taylor & Francis.

Bibliographic Details

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

Informa UK Limited

Biochemistry, Genetics and Molecular Biology; Nursing; Medicine

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