β2-Microglobulin (β2M), 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 β2M in the development of lung emphysema. Here, we found that concentrations of β2M 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 β2M was significantly higher in lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%, P < 0.01). Immunofluorescence showed that β2M was mainly expressed in prosurfactant protein C-positive (pro-SPC+) alveolar epithelial cells and CD14+ macrophages. Exposure to recombinant human β2M 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-β2M antibody. However, anti-β2M antibody did not attenuate the elevated production of IL-1β, IL-6, and TNF-α in A549 cells that were exposed to CSE. Immunofluorescence showed that colocalization of β2M, and the hemochromatosis gene (HFE) protein was observed on A549 cells. These data suggest β2M might participate in the development of lung emphysema through induction of lung epithelial cell senescence and inhibition.
Regulation of lung epithelial cell senescence in smoking-induced COPD/emphysema by microR-125a-5p via Sp1 mediation of SIRT1/HIF-1a
