Exposure to
chrysotile asbestos exposure is associated with an increased risk of mortality in combination with
pulmonary diseases including
lung cancer,
mesothelioma and
asbestosis. Multiple mechanisms by which
chrysotile asbestos fibers induce
pulmonary disease have been identified, however the role of apoptosis in human lung alveolar epithelial cells (AEC) has not yet been fully explored. Accumulating evidence implicates AEC apoptosis as a crucial event in the development of both
idiopathic pulmonary fibrosis and
asbestosis. The aim of the present study was to determine whether
chrysotile asbestos induces mitochondria‑regulated (intrinsic) AEC apoptosis and, if so, whether this induction occurs via the activation of mitogen‑activated
protein kinases (MAPK). Human A549 bronchoalveolar carcinoma‑derived cells with alveolar epithelial type II‑like features were used. The present study showed that
chrysotile asbestos induced a dose‑ and time‑dependent decrease in A549 cell viability, which was accompanied by the activation of the MAPK c‑Jun N‑terminal
kinases (JNK), but not the MAPKs extracellular signal‑regulated
kinase 1/2 and p38.
Chrysotile asbestos was also shown to induce intrinsic AEC apoptosis, as evidenced by the upregulation of the pro‑apoptotic genes Bax and Bak, alongside the activation of caspase‑9, poly (ADP‑ribose)
polymerase (PARP), and the release of
cytochrome c. Furthermore, the specific JNK inhibitor
SP600125 blocked
chrysotile asbestos‑induced JNK activation and subsequent apoptosis, as assessed by both caspase‑9 cleavage and PARP activation. The results of the present study demonstrated that
chrysotile asbestos induces intrinsic AEC apoptosis by a JNK‑dependent mechanism, and suggests a potential novel target for the modulation of
chrysotile asbestos‑associated
lung diseases.