Masking of Corticosteroid-induced Inhibition of NF-κB activation by (S)-Albuterol in Human Airway...
Transcript of Masking of Corticosteroid-induced Inhibition of NF-κB activation by (S)-Albuterol in Human Airway...
![Page 1: Masking of Corticosteroid-induced Inhibition of NF-κB activation by (S)-Albuterol in Human Airway Smooth Muscle Cells and Human Blood Lymphocytes](https://reader036.fdocument.org/reader036/viewer/2022082903/575091251a28abbf6b9bce85/html5/thumbnails/1.jpg)
544 Quality of Life of Children with Allergic Diseases
Y. Adachi1, Y. Okabe1, T. Itazawa1, Y. S. Adachi1, M. Nakabayashi1, T.
Fuchizawa1, T. Miyawaki1, H. Odajima2; 1Dept of Pediatrics, Toyama
Medical & Pharmaceutical University, Toyama, JAPAN, 2Dept of Pedi-
atrics, Fukuoka National Hospital, Fukuoka, JAPAN.
RATIONALE: It has not been well evaluated how allergic diseases
impair the quality of life (QOL) of children compared with healthy ones.
METHODS: We carried out a cross-sectional survey among the younger
children aged 6-8 yr and elder ones aged 13-15 yr in a Japanese prefec-
ture (Toyama), using a generic QOL questionnaire; Kid-KINDL®. The
survey was performed since May through August 2005. Asthma (A),
allergic rhinitis (R), and eczema (E) were defined based on the ISSAC
questionnaire.
RESULTS: During the previous one year, 13.0, 38.6, and 19.4% of the
younger children (n=1771), and 6.1, 57.4, and 13.5% of the elder ones
(n=942) had been symptomatic for A, R, E, respectively. On the other
hand, 42.3% of the younger children and 27.7% of the elder ones had
never experienced any allergic symptoms in their lives. Comparing to
these healthy children, the symptomatic children had impaired QOL,
especially in “physical” and “friend” parts. The number of the
impaired scales in the older group was higher than that of the younger
one.
CONCLUSIONS: Many children are suffered from allergic symptoms.
Allergic diseases have a substantial impact on the QOL in children com-
pared with healthy children. Supported by a grant from Japanese Ministry
of Health, Labour and Welfare for Japanese Asthma Survey Group.
545 Impaired Quality of Life in Child Asthmatics in Tokyo, Japan
N. Kojima1,2, Y. Ohya1,2, M. Futamura1,2, M. Akashi1,2, K. Akiyama2, K.
Takahashi2, T. Nakagawa2, F. Kobayashi2, A. Eboshida2, H. Nakamura2,
H. Odajima2, Y. Adachi2, A. Akasawa1,2; 1National Center for Child
Health and Development, Tokyo, JAPAN, 2Japanese Asthma Survey
Group, Tokyo, JAPAN.
RATIONALE: Asthma is the most common chronic diseases in school-
aged children in Japan. Measuring of QOL is important to evaluate their
school life.
METHODS: School based survey was conducted by using KINDL-R
quality of life(QOL) questionnaire and ISAAC questionnaire for children
of 6-7 years old and 13-14 years old from May to June in 2005. Randomly
selected public schools managed by local governments in Tokyo joined
this investigation.
RESULTS: Response rate of these questionnaire was 86%(22645 chil-
dren) in 6-7 year old group and 64%(12879 children) in 13-14 year old
group. Comparing asthmatics with non-asthmatics in the same age,
QOL of children with asthma was significantly impaired (younger
group: 96.7 vs 98.6, p<.001, elder group: 78.2 vs 83.0, p<.001). In addi-
tion, QOL of children was significantly impaired by severity (severe
asthmatics, moderate ones, mild ones and non-asthmatics was 95.1,
95.8, 97.9 and 98.6 respectively in younger children, and 76.2, 78.4,
78.3 and 83.0 respectively in elder ones. p<.001). Especially QOL of
children with exercise-induced asthma (EIA) were more significantly
impaired than ones without EIA (younger group: 95.7 vs 97.1, p<.001,
elder group: 77.2 vs 81.1, p<0.01) and showed lower score in the cate-
gories of school, emotional well-being and physical well-being than
those without EIA.
CONCLUSIONS: This is the first investigation to focus on the QOL
comparison between Japanese children with asthma and those without it.
QOL of children was impaired by having asthma even in the mild cases
and more severely disturbed in elder cases and the cases with EIA.
Funding: Ministry of Health, Labour and Welfare
546 Masking of Corticosteroid-induced Inhibition of NF-�B acti-vation by (S)-Albuterol in Human Airway Smooth MuscleCells and Human Blood Lymphocytes
D. K. Agrawal1, G. Cheng1, P. W. Kelbe2; 1Biomedical Sciences,
Creighton University School of Medicine, Omaha, NE, 2Medical Liason,
Sepracor Inc., Marlborough, MA.
RATIONALE: Pro-constrictory and pro-inflammatory properties of (S)-
albuterol have been widely reported. However, underlying mechanisms
are unclear. We examined the effect of (S)-albuterol on corticosteroid-
induced inhibition of NF-�B in human airway smooth muscle cells
(HASMCs) and human blood lymphocytes. We also investigated if (S)-
Albuterol synergized response of TNF-� to stimulate NF-�B in
HASMCs.
METHODS: Lymphocytes were purified from the blood of normal vol-
unteers using Percoll density gradient followed by non-adherence to cul-
ture dish. Primary HASMCs were grown in culture. Lymphocytes or
HASMCs were treated with various concentrations of albuterol enan-
tiomers (0.1 - 1.0 microM). Dexamethasone (1 microM) and TNF-� (100
nM) were used to stimulate cells. Activity of NF-�B was measured by
Western blot and TransAM method using antibodies to p65.
RESULTS: Both (RS) and (S)-albuterol induced NF-�B activation in
both human blood lymphocytes and HASMCs in a dose-dependent man-
ner. However (R)-albuterol (up to 10 microM concentration) had no
effect. Short-term exposure (90 minutes) of the cells to dexamethasone
significantly attenuated (25-35%) the activation of NF-�B by (S)- and
(RS)-albuterol. Interestingly, chronic exposure of the cells to (S)-albuterol
for 8-24 hours significantly attenuated (42-60%) the effect of dexametha-
sone to inhibit NF-�B activity. However, prior exposure of the cells to
(R)-albuterol did not affect dexamethasone-induced inhibition of NF-�B.
TNF-� induced NF-�B activity and this effect was amplified by
(S)-albuterol (0.1 and 1.0 microM).
CONCLUSIONS: Since NF-�B is a potent transcription factor involved
in airway inflammation, these data suggest that (S)-albuterol can either
mask or antagonize the beneficial effect of dexamethasone and amplify
the adverse effect of inflammatory cytokines.
Funding: Sepracor Inc.
547 Expression of Cysteinyl Leukotriene Receptors by CD34+Umbilical Cord Blood (CB) - Progenitor Cells: Relevance toAtopic Development
J. A. ROA, A. J. BAATJES, L. D. SALEH, M. M. CYR, G. M. GAU-
VREAU, J. A. DENBURG; Division of clinical immunology and allergy,
department of medicine, FACULTY OF HEALTH SCIENCES, McMAS-
TER UNIVERSITY, HAMILTON, ON, CANADA.
RATIONALE: The cysteinyl leukotrienes (cysLTs) are potent, bioactive
lipids that contribute to allergic and inflammatory diseases. Pharmacolog-
ical studies have identified two classes of cysLT receptors (cysLTR1 and
cysLTR2), which are expressed on a variety of cell types, including
human peripheral blood CD34+ cells. However, no information is yet
available regarding cysLTR expression on human umbilical CB progeni-
tor cells. We examined the expression of cysLTR1 and cysLTR2 on
human CB CD34+ progenitor cells, in order to be able to assess their
potential relevance to the development of atopy.
METHODS: Non-adherent mononuclear cells (NAMNC) were obtained
from human CB. Flow cytometric staining of these cells was performed
using monoclonal antibodies to CD34 and CD45, and polyclonal rabbit
antibodies selective and specific for cysLTR1 and cysLTR2 (Caymen
Chemical). Flow cytometric data were collected on a three-colour BD
FACScan cytometer. WinMDI analysis software was used to evaluate the
expression of cysLTR1 and cysLTR2.
RESULTS: The mean expression on CD34+/CD45+ progenitor cells of
cysLTR1 was 35% (SD ± 11; n=5) with a range of 21% to 44% and a
median of 35. The mean expression of cysLTR2 was 40% (SD ± 20; n=5)
with a range of 26% to 71% and a median of 36%.
S140 Abstracts J ALLERGY CLIN IMMUNOL
FEBRUARY 2006
SU
ND
AY