TSPO is a new anti-inflammatory target in the airway of COPD - 04/04/15

Chronic obstructive pulmonary disease (COPD) is a major public health problem. It is well-known that COPD is characterized by a systemic inflammatory response. Recent studies have shown that the 18kDa translocator protein (TSPO) – also known as the peripheral benzodiazepine receptor, plays a key role in the regulation of immune function and inflammation. Benzodiazepine use is high among adults with COPD.

The aim of this study was to investigate TSPO expression in COPD biopsies and to establish 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 morphometric analysis.

TSPO agonist (Ro5-4864) and antagonist (PK-11195) were used on NCI-H292 and air liquid interface (ALI) cultures of bronchial epithelial cells. Cellular TSPO expression was assessed by PCR. Cigarette smoke extract (CSE)-induced epithelial inflammation and cell viability were assessed by interleukin 8 (IL-8) and lactate deshydrogenase assays respectively.

TSPO expression was mainly detected in bronchial epithelium and inflammatory cells. Expression levels were independently associated with COPD status (P-value 0.01827) and age (P-value 0.00203). There was no association with benzodiazepine intake.

NCI-H292 and airway epithelial cells cultivated at ALI both expressed TSPO. In NCI-H292, Ro5-4864 (10⁻⁹M) increased IL-8 release. PK-11195 (10⁻⁹M) partially prevented CSE-induced IL-8 release.

TSPO appears to play an important role in COPD airway epithelial cells. TSPO antagonist PK-11195 decreased CSE-induced inflammation.

TSPO antagonist should be further evaluated as a potential future COPD treatment.