TY - JOUR
T1 - Interleukin-9 induces goblet cell hyperplasia during repair of human airway epithelia
AU - Vermeer, Paola D.
AU - Harson, Robert
AU - Einwalter, Lisa A.
AU - Moninger, Tom
AU - Zabner, Joseph
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - Asthma is characterized by airway inflammation, smooth muscle hyperreactivity, and airway remodeling with excessive mucus production. The effect cytokines like interleukin (IL)-9 have on airway epithelia has been addressed using murine models of asthma, as well as transgenic and knockout mice. Though highly informative, differences exist between mouse and human airway epithelia, including cellular composition (e.g., Clara cells) and stem cell/plasticity capabilities. Therefore, to address cytokine effects on human airway epithelia, we have used a primary model system to ask whether IL-9 can alter cell fates of human airway epithelia. Here, we show that IL-9 has little effect on fully differentiated ciliated human airway epithelia. However, in the setting of airway injury repair, IL-9 results in goblet cell hyperplasia. A similar response was observed when the epithelium was exposed to IL-9 before it became fully differentiated. Moreover, exposure to IL-9 resulted in increased lysozyme and mucus production by the epithelia. Thus, a combination of IL-9 and mechanical injury can explain, in part, goblet cell hyperplasia that is evident in the lungs of individuals with asthma. These data suggest that interventions that limit airway epithelial damage, block IL-9, or modulate the repair process should result in decreased airway remodeling and prevent the chronic manifestations of this disease.
AB - Asthma is characterized by airway inflammation, smooth muscle hyperreactivity, and airway remodeling with excessive mucus production. The effect cytokines like interleukin (IL)-9 have on airway epithelia has been addressed using murine models of asthma, as well as transgenic and knockout mice. Though highly informative, differences exist between mouse and human airway epithelia, including cellular composition (e.g., Clara cells) and stem cell/plasticity capabilities. Therefore, to address cytokine effects on human airway epithelia, we have used a primary model system to ask whether IL-9 can alter cell fates of human airway epithelia. Here, we show that IL-9 has little effect on fully differentiated ciliated human airway epithelia. However, in the setting of airway injury repair, IL-9 results in goblet cell hyperplasia. A similar response was observed when the epithelium was exposed to IL-9 before it became fully differentiated. Moreover, exposure to IL-9 resulted in increased lysozyme and mucus production by the epithelia. Thus, a combination of IL-9 and mechanical injury can explain, in part, goblet cell hyperplasia that is evident in the lungs of individuals with asthma. These data suggest that interventions that limit airway epithelial damage, block IL-9, or modulate the repair process should result in decreased airway remodeling and prevent the chronic manifestations of this disease.
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U2 - 10.1165/rcmb.4887
DO - 10.1165/rcmb.4887
M3 - Article
C2 - 12594054
AN - SCOPUS:0037372482
SN - 1044-1549
VL - 28
SP - 286
EP - 295
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 3
ER -