| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the North Carolina State University (Mr. Booth, Ms. Akley, and Drs. Macchione, Adler, and Martin), Raleigh, NC; and National Institute of Environmental Health Sciences (Dr. Bonner), Research Triangle Park, NC.
Correspondence to: Linda D. Martin, PhD, Research Assistant Professor of Cell Biology, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough St, Raleigh, NC 27606
Subepithelial
fibrosis is a prominent feature of the remodeled asthmatic airway. The
cytokine interleukin (IL)-13, implicated as a mediator in the
development of asthma, induces a significant degree of subepithelial
fibrosis in the lungs of transgenic mice. Since IL-13 has been shown to
exert effects on the airway epithelium, including the development of a
mucous phenotype, we have begun to determine whether IL-13 provokes
production of factors from the epithelium that could elicit the
observed subepithelial fibrotic response. In the studies reported
herein, injured airways with regions of regenerating/differentiating
cells and regions of normal fully differentiated cells have been
mimicked by examining the effects of IL-13 on normal human bronchial
epithelial cells during mucociliary differentiation in air/liquid
interface culture. Exposure of normal human bronchial epithelial cells
to IL-13 resulted in increased production of soluble transforming
growth factor (TGF)-
, with the growth factor interacting in an
autocrine manner with the epidermal growth factor receptor. Production
of soluble TGF- was very rapid, with a threefold increase observed
in response to IL-13 (10 ng/mL) by 1 h of exposure. Continuous
exposure to IL-13 throughout the course of mucociliary differentiation
(a total of 10 days) resulted in a twofold increase in cell number by
day 7 when cells are differentiated. Exposure to IL-13 (10 ng/mL;
24 h) provoked a threefold increase in proliferation once the
cells were differentiated, an effect that could be duplicated in
differ- entiated, but not undifferentiated cells, by the
direct addition of TGF- (5 ng/mL or 25 ng/mL; 24 h).
Proliferation of differentiated cells in response to continuous IL-13
treatment was followed 2 days later by a decrease in proliferation
compared to control mice. Soluble TGF-, however, continued to be
produced from these nonproliferating cultures. Thus, an increase in
soluble TGF- in response to IL-13 may serve to promote proliferation
of injured epithelial cells in an autocrine manner. Once this
proliferative effect is no longer necessary, the soluble TGF- may
promote proliferation of other cells. These data suggest that any
injury to the airway epithelium resulting in the production of IL-13
from infiltrating inflammatory cells may provoke the release of soluble
TGF- from the airway epithelium. The availability of this growth
factor may contribute to the subepithelial fibrosis observed in chronic
asthma.
Footnotes
Abbreviations: IL = interleukin; TGF = transforming growth factor
Supported by National Institutes of Health grants HL36982 and HL09869, and a grant from the state of North Carolina.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
