ß2-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence.
Am J Physiol Lung Cell Mol Physiol
; 312(5): L669-L677, 2017 05 01.
Article
em En
| MEDLINE
| ID: mdl-28213472
ABSTRACT
ß2-Microglobulin (ß2M), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of ß2M in the development of lung emphysema. Here, we found that concentrations of ß2M in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 vs. 1.42 ± 0.06 mg/l, P < 0.01). Moreover, the expression of ß2M was significantly higher in lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%, P < 0.01). Immunofluorescence showed that ß2M was mainly expressed in prosurfactant protein C-positive (pro-SPC+) alveolar epithelial cells and CD14+ macrophages. Exposure to recombinant human ß2M and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-ß2M antibody. However, anti-ß2M antibody did not attenuate the elevated production of IL-1ß, IL-6, and TNF-α in A549 cells that were exposed to CSE. Immunofluorescence showed that colocalization of ß2M, and the hemochromatosis gene (HFE) protein was observed on A549 cells. These data suggest ß2M might participate in the development of lung emphysema through induction of lung epithelial cell senescence and inhibition.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Enfisema Pulmonar
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Microglobulina beta-2
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Senescência Celular
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Células Epiteliais
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Pulmão
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Physiol Lung Cell Mol Physiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article