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Extracellular Vesicles Derived from Gram-Negative Bacteria, such as Escherichia coli, Induce Emphysema Mainly via IL-17A-Mediated Neutrophilic Inflammation

Title
Extracellular Vesicles Derived from Gram-Negative Bacteria, such as Escherichia coli, Induce Emphysema Mainly via IL-17A-Mediated Neutrophilic Inflammation
Authors
Kim, You-SunLee, Won-HeeChoi, Eun-JeongChoi, Jun-PyoHeo, Young JooGho, Yong SongJee, Young-KooOh, Yeon-MokKim, Yoon-Keun
Ewha Authors
김윤근최준표
SCOPUS Author ID
김윤근scopusscopus
Issue Date
2015
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
0022-1767JCR Link1550-6606JCR Link
Citation
vol. 194, no. 7, pp. 3361 - 3368
Publisher
AMER ASSOC IMMUNOLOGISTS
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Recent evidence indicates that Gram-negative bacteria-derived extracellular vesicles (EVs) in indoor dust can evoke neutrophilic pulmonary inflammation, which is a key pathology of chronic obstructive pulmonary disease (COPD). Escherichia coli is a ubiquitous bacterium present in indoor dust and secretes nanometer-sized vesicles into the extracellular milieu. In the current study, we evaluated the role of E. coli-derived EVs on the development of COPD, such as emphysema. E. coli EVs were prepared by sequential ultrafiltration and ultracentrifugation. COPD phenotypes and immune responses were evaluated in C57BL/6 wild-type (WT), IFN-gamma-deficient, or IL-17A-deficient mice after airway exposure to E. coli EVs. The present study showed that indoor dust from a bed mattress harbors E. coli EVs. Airway exposure to E. coli EVs increased the production of proinflammatory cytokines, such as TNF-alpha and IL-6. In addition, the repeated inhalation of E. coli EVs for 4 wk induced neutrophilic inflammation and emphysema, which are associated with enhanced elastase activity. Emphysema and elastase activity enhanced by E. coli EVs were reversed by the absence of IFN-gamma or IL-17A genes. In addition, during the early period, lung inflammation is dependent on IL-17A and TNF-alpha, but not on IFN-gamma, and also on TLR4. Moreover, the production of IFN-gamma is eliminated by the absence of IL-17A, whereas IL-17A production is not abolished by IFN-gamma absence. Taken together, the present data suggest that E. coli-derived EVs induce IL-17A-dependent neutrophilic inflammation and thereby emphysema, possibly via upregulation of elastase activity.
DOI
10.4049/jimmunol.1402268
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의학전문대학원 > 의학과 > Journal papers
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