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Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma

Title
Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma
Authors
Kim, YKOh, SYJeon, SGPark, HWLee, SYChun, EYBang, BLee, HSOh, MHKim, YSKim, JHGho, YSCho, SHMin, KUKim, YYZhou Zhu
POSTECH Authors
Kim, YKGho, YS
Date Issued
Jan-2007
Publisher
AMER ASSOC IMMUNOLOGISTS
Abstract
Allergic asthma is characterized by airway inflammation initiated by adaptive immune responses to aeroallergens. Recent data suggest that severe asthma may be a different form of asthma rather than an increase in asthma symptoms and that innate immune responses to LPS can modulate adaptive immune responses to allergens. In this study, we evaluated the hypothesis that airway exposure to different doses of LPS induces different form of asthma. Our study showed that neutrophilic inflammation and IFN-gamma expression were higher in induced sputum from severe asthma patients than from mild to moderate asthmatics. Animal experiments indicated that allergen sensitization with low-dose LPS (0.1 mu g) induced type 2 asthma phenotypes, i.e., airway hyper-responsiveness, eosinophilic inflammation, and allergen-specific IgE up-regulation. In contrast, allergen sensitization with high-dose LPS (10 mu g) induced asthma phenotypes, i.e., airway hyperresponsiveness and noneosinophilic inflammation that were not developed in IFN-gamma-deficient mice, but unaffected in the absence of IL-4. During the allergen sensitization period, TNF-alpha expression was found to be enhanced by both low- and high-dose LPS, whereas IL-12 expression was only enhanced by high-dose LPS. Interestingly, the asthma phenotypes induced by low-dose LPS, but not by high-dose LPS, were completely inhibited in TNF-a receptor-deficient mice, whereas the asthma phenotypes induced by high-dose LPS were abolished in the homozygous null mutation of the STAT4 gene. These findings suggest that airway exposure levels of LPS induces different forms of asthma that are type 1 and type 2 asthma phenotypes by high and low LPS levels, respectively.
Keywords
HOUSE-DUST ENDOTOXIN; T-CELL DEVELOPMENT; INTERFERON-GAMMA; DENDRITIC CELLS; ALLERGIC-ASTHMA; RESPONSES; MICE; HYPERRESPONSIVENESS; INFLAMMATION; ANTIGEN
URI
http://oasis.postech.ac.kr/handle/2014.oak/29482
ISSN
0022-1767
Article Type
Article
Citation
JOURNAL OF IMMUNOLOGY, vol. 178, no. 8, page. 5375 - 5382, 2007-01
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 GHO, YONG SONG
Dept of Life Sciences
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