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

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Authors
Kim, Yoon-Keun; Oh, Sun-Young; Jeon, Seong Gyu; Park, Heung-Woo; Lee, Soo-Yeon; Chun, Eun-Young; Bang, Boram; Lee, Hyun-Seung; Oh, Min-Hee; Kim, You-Sun; Kim, Jong-Hoon; Gho, Yong Song; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Zhu, Zhou
Issue Date
2007-04-04
Publisher
American Association of Immunologists
Citation
J Immunol. 2007 Apr 15;178(8):5375-82.
Keywords
AdultAgedAnimalsAsthma/*etiology/immunologyBronchial Hyperreactivity/etiologyFemaleHumansInterferon-gamma/genetics/physiologyInterleukin-12/biosynthesisLipopolysaccharides/*toxicityMaleMiceMice, Inbred BALB CMice, Inbred C57BLMiddle AgedOvalbumin/immunologyRNA, Messenger/analysisReceptors, Tumor Necrosis Factor/physiologySTAT4 Transcription Factor/physiologySignal TransductionTh1 Cells/*immunologyTh2 Cells/*immunologyTransforming Growth Factor beta1/biosynthesisTumor Necrosis Factor-alpha/biosynthesis
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 microg) induced type 2 asthma phenotypes, i.e., airway hyperresponsiveness, eosinophilic inflammation, and allergen-specific IgE up-regulation. In contrast, allergen sensitization with high-dose LPS (10 microg) 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-alpha 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.
ISSN
0022-1767 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17404323

http://hdl.handle.net/10371/29631
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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