The effect of IL-13 and IL-13R130Q, a naturally occurring IL-13 polymorphism, on the gene expression of human airway smooth muscle cells.
BACKGROUND
Growing evidence shows that interleukin 13 (IL-13) may play an essential role in the development of airway inflammation and bronchial hyper-responsiveness (BHR), two defining features of asthma. Although the underlying mechanisms remain unknown, a number of reports have shown that IL-13 may exert its deleterious effects in asthma by directly acting on airway resident cells, including epithelial cells and airway smooth muscle cells. In this report, we hypothesize that IL-13 may participate in the pathogenesis of asthma by activating a set of "pro-asthmatic" genes in airway smooth muscle (ASM) cells.


METHODS
Microarray technology was used to study the modulation of gene expression of airway smooth muscle by IL-13 and IL-13R130Q. TaqMan Real Time PCR and flow cytometry was used to validate the gene array data.


RESULTS
IL-13 and the IL-13 polymorphism IL-13R130Q (Arg130Gln), recently associated with allergic asthma, seem to modulate the same set of genes, which encode many potentially interesting proteins including vascular cellular adhesion molecule (VCAM)-1, IL-13Ralpha2, Tenascin C and Histamine Receptor H1, that may be relevant for the pathogenesis of asthma.


CONCLUSIONS
The data supports the hypothesis that gene modulation by IL-13 in ASM may be essential for the events leading to the development of allergic asthma.
Syed
Farhat
F
Centocor Inc,, 200 Great Valley Parkway, Malvern, PA 19355, USA. fsyed@cntus.jnj.com
Panettieri
Reynold A
RA
Tliba
Omar
O
Huang
Chris
C
Li
Katherine
K
Bracht
Michelle
M
Amegadzie
Bernard
B
Griswold
Don
D
Li
Li
L
Amrani
Yassine
Y
D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011110:Polymorphism, Genetic; D014132:Trachea / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D018793:Interleukin-13; D019010:Vascular Cell Adhesion Molecule-1