As Maureen points out - there will probably be several
"causes" of asthma identified. Infections will surely will
be amonst them as will genetics and I'm sure environmental
factors will also have a role. Watch out for anyone claiming
a single cause for all of it.

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From the August 5, 2004 New England Journal Of Medicine.

Dysfunctional Interaction of C/EBP and the Glucocorticoid
Receptor in Asthmatic Bronchial Smooth-Muscle Cells

Michael Roth, Ph.D., Peter R.A. Johnson, Ph.D., Peter
Borger, Ph.D., Michel P. Bihl, Ph.D., Jochen J. R?diger,
M.D., Gregory G. King, M.D., Qi Ge, M.Sc., Katrin
Hostettler, M.D., Janette K. Burgess, Ph.D., Judith L.
Black, M.B., B.S., Ph.D., and Michael Tamm, M.D.

ABSTRACT
Background Increased proliferation of bronchial
smooth-muscle cells may lead to increased muscle mass in the
airways of patients with asthma. The antiproliferative
effect of glucocorticoids in bronchial smooth-muscle cells
in subjects without asthma is mediated by a complex of the
glucocorticoid receptor and the CCAAT/enhancer binding
protein  (C/EBP). We examined the signaling pathway
controlling the inhibitory effect of glucocorticoids on cell
proliferation and interleukin-6 synthesis in bronchial
smooth-muscle cells of subjects with asthma and those
without asthma.
Methods Lines of bronchial smooth-muscle cells were
established from cells from 20 subjects with asthma, 8
subjects with emphysema, and 26 control subjects. Cell
proliferation was determined by means of cell counts and
[3H]thymidine incorporation. Signal transduction was studied
by means of an electrophoretic DNA mobility-shift assay, a
supershift electrophoretic-mobility assay, immunoblotting,
use of C/EBP antisense oligonucleotides, and use of a human
C/EBP expression vector. Interleukin-6 release was
determined by means of an enzyme-linked immunosorbent assay.
Results Glucocorticoids activated the glucocorticoid
receptor and inhibited serum-induced secretion of
interleukin-6 in bronchial smooth-muscle cells from both
subjects with asthma and those without asthma; however,
glucocorticoids inhibited proliferation only in bronchial
smooth-muscle cells from subjects without asthma. C/EBP
protein was detected by immunoblotting in all bronchial
smooth-muscle cells from subjects without asthma but not in
those with asthma, whereas the protein was expressed in
lymphocytes from both groups of subjects. C/EBP antisense
oligonucleotides or the glucocorticoid-receptor inhibitor
mifepristone reversed the antiproliferative effect of
glucocorticoids in bronchial smooth-muscle cells from
subjects without asthma. When bronchial smooth-muscle cells
from subjects with asthma were transiently transfected with
an expression vector for human C/EBP, two forms of the
protein were expressed, and subsequent administration of
glucocorticoids inhibited cell proliferation.
Conclusions We hypothesize that a cell-type-specific absence
of C/EBP is responsible for the enhanced proliferation of
bronchial smooth-muscle cells derived from subjects with
asthma and that it explains the failure of glucocorticoids
to inhibit proliferation in vitro.

Source Information
From the Department of Pharmacology and the Woolcock
Institute of Medical Research, University of Sydney, Sydney,
Australia (M.R., P.R.A.J., P.B., G.G.K., Q.G., K.H., J.K.B.,
J.L.B.); and the Departments of Research and Internal
Medicine, Pulmonary Cell Research, University Hospitals
Basel, Basel, Switzerland (M.R., M.P.B., J.J.R., M.T.).

Drs. Johnson, Borger, Black, and Tamm contributed equally to
this article.