JAK–STAT pathway activation in COPD

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung, most commonly resulting from cigarette smoke exposure, characterised by a largely irreversible and progressive airflow limitation [1, 2]. Currently, there are no disease-modifying therapies to prevent the relentless disease progression in patients with COPD. As a consequence, COPD is associated with high mortality and increasing prevalence worldwide [2]. Therefore, significant research effort has been directed to understanding the mechanism by which cigarette smoke exposure leads to the inflammation seen in COPD in the hope of discovering novel, effective anti-inflammatory therapies to tackle underlying pathogenic mechanisms. Cytokines are thought to be critical orchestrators of the persistent inflammation seen in several inflammatory diseases, including COPD. Many of these cytokines signal through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway and/or are produced as a result of JAK–STAT pathway signalling [3]. Thus, currently, there is considerable interest in developing JAK–STAT inhibitors as a potential treatment for COPD. However, there are no published studies that have comprehensively investigated the activation of all the STAT family members in tissue from COPD patients. Therefore, the aim of our study was to determine the extent of JAK–STAT pathway activation by detecting the presence of phosphorylated STAT proteins 1–6 in lung tissue from nonsmokers, healthy smokers and COPD patients (from transplant surgery) by Western blotting and immunohistochemistry (IHC). The hope was that this would provide important information regarding the role of the JAK–STAT pathway in COPD, which may in turn be useful in the development of novel treatments for COPD. JAK–STAT pathway activation in the lung of COPD patients