TSPO a new anti-inflammatory target in the airway of COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by a systemic inflammatory response. The 18kDa translocator protein (TSPO), known as the Peripheral Benzodiazepine Receptor, plays a key role in the regulation of immune function and inflammation. Benzodiazepines are widely used among adults with COPD and their impacts on TSPO and airway physiology are unknown. In this study, we investigated TSPO expression in COPD biopsies and established an in vitro model to examine the role of TSPO in COPD inflammation. Samples were obtained from lung surgery of healthy-smokers and COPD patients. TSPO expression was evaluated using immunohistochemistry and quantified by morphometric analysis. TSPO agonist (Ro5-4864) and antagonist (PK-11195) were used on air-liquid interface (ALI) cultures of human bronchial epithelial cells. Cellular TSPO expression was assessed by RTqPCR and immunofluorescence. Cigarette smoke extract (CSE)-induced epithelial inflammation and cell viability were assessed through interleukin 8 (IL-8) and lactate deshydrogenase release assays respectively. On biopsies, TSPO expression was mainly detected in bronchial epithelial and inflammatory cells. Expression was independently associated with COPD status ( p = 0.0127). There was no association with declared benzodiazepine intake. ALI airway epithelial cells culture expressed TSPO as confirmed by RTqPCR and immunofluorescence. Ro5-4864 (10 −9 M) increased IL-8 release while PK-11195 (10 −9 M) partially prevented CSE-induced IL-8 release. TSPO appears to play a significant role in COPD airway epithelial cells. TSPO antagonist PK-11195 decreased CSE-induced inflammation therefore it should be further evaluated as a potential target for COPD management.