Cigarette smoke induces apoptosis via 18 kDa translocator protein in human bronchial epithelial cells

Aims: The 18 kDa translocator protein (TSPO) - also known as peripheral benzodiazepine receptor, is found to be expressed in lung epithelium and pneumocytes, which is closely associated with the mitochondrial permeability transition pore (mPTP) and apoptosis. Cigarette smoking, a key risk factor for the development of chronic obstructive pulmonary disease (COPD), is known to induce apoptosis. We aimed to investigate TSPO subcellular localization and to examine whether cigarette smoke medium (CSM) induce apoptosis via TSPO in airway epithelial cells. Main methods: TSPO subcellular localization and expression were evaluated using immunofluorescent staining and Western blot analysis respectively. TSPO ligands either PK 11195 (a specific antagonist) or AC-5216 (a specific agonist) were pre-incubated in human bronchial epithelial cells before treating with 2% CSM for measurements of apoptotic cells, mitochondrial membrane potential (Delta Psi m), cytoplasmic/mitochondrial reactive oxygen species (ROS) and inflammatory marker interleukin (IL)-8 respectively. Key findings: TSPO was localized around the nucleus and overlapped with mitochondria in BEAS-2B cells. CSM caused an increase in apoptotic cells along with elevation of TSPO protein expression. Pretreatment of PK 11195 suppressed while AC-5216 potentiated CSM-induced apoptosis, collapse of O Delta Psi m, elevation of cytoplasmic/mitochondrial ROS levels and IL-8 release. In support, knockdown of TSPO caused a significant suppression of CSM-induced IL-8 release in BEAS-2B cells. Significance: The findings suggest that TSPO may play a crucial role in the regulation of cigarette smoke-induced mitochondrial dysfunction via mPTP. Therefore, the development of specific TSPO antagonists like PK11195 may be beneficial to combat smoking-related diseases, such as COPD.

Automated summary

TSPO is closely associated with mitochondrial permeability transition pore (mPTP) and apoptosis in lung epithelium. Cigarette smoke medium induces apoptosis and TSPO plays a crucial role in regulating mitochondrial dysfunction. Targeting TSPO with specific antagonists may be beneficial in combating smoking-related diseases like COPD.