IL-8 and TSLP production from epithelial cells in IL-17A mediated airway inflammation of COPD patients

IL-17A plays a key role in the persistence of airway inflammation, oxidative stress, and in the reduction of steroid-sensitivity in COPD. Very few studies describe IL-17A activities in airway inflammation during COPD. We measured the levels of IL-17A in sputum supernatants (ISSs) from healthy controls (HC) (n=10), healthy smokers (HS) (n=10), and COPD patients (n=10). Furthermore, human bronchial epithelial cells (16HBE) were stimulated (4 hrs and 24 hrs, 37°C) with ISSs from HC (n=6), HS (n=6), or COPD (n=6), as well as with human recombinant (hr) IL-17A. IL-8 and TSLP were evaluated in 16HBE supernatants and in cell lysates by ELISA and by WB, respectively. HDAC2 activity was evaluated in nuclear cell lysates by a commercial colorimetric assay kit. IL-17A was increased in ISSs from COPD patients and HS subjects when compared with HC. IL-8 and TSLP were higher in cell lysates and supernatants of 16HBE stimulated with ISSs from COPD and HS than in cell lysates and supernatants of 16HBE stimulated with ISSs from HC and in the cells stimulated with hrIL-17A when compared with untreated cells. HDAC2 activity was reduced in nuclear cell lysates of 16HBE stimulated with hrIL-17A when compared with untreated cells. Our findings suggest that IL-17A present in the airway of COPD patients is able to increase the IL-8 and TSLP production due to a markedly reduction of the HDAC2 activity.