title: Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma.
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.
authors.affiliation: Department of Life Science, Postech Biotech Center, Pohang University of Science and Technology, Namgu, Pohang, Gyeongbuk, Republic of Korea.
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Oh
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Chun
authors.forename: Boram
authors.initials: B
authors.lastname: Bang
authors.forename: Hyun-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Oh
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Kyung-Up
authors.initials: KU
authors.lastname: Min
authors.forename: You-Young
authors.initials: YY
authors.lastname: Kim
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000209:etiology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D050797:STAT4 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D050797:STAT4 Transcription Factor; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin