PT - JOURNAL ARTICLE AU - Mirai Mizutani AU - Julie Bérubé AU - Heather G. Ahlgren AU - Joanie Bernier AU - Elias Matouk AU - Dao Nguyen AU - Simon Rousseau TI - Corticosteroid-resistant inflammatory signalling in <em>Pseudomonas</em>-infected bronchial cells AID - 10.1183/23120541.00144-2016 DP - 2017 Apr 01 TA - ERJ Open Research PG - 00144-2016 VI - 3 IP - 2 4099 - http://openres.ersjournals.com/content/3/2/00144-2016.short 4100 - http://openres.ersjournals.com/content/3/2/00144-2016.full SO - erjor2017 Apr 01; 3 AB - Decreasing the inflammatory response that leads to tissue damage during cystic fibrosis (CF) lung disease has been a long-standing goal of CF therapy. While corticosteroids are widely used anti-inflammatory drugs, their efficacy in CF lung disease remains debated. The complex interaction between the colonising bacteria and the host environment may impact corticosteroid responsiveness.In this study, sputum samples from adult CF patients were collected at baseline and during pulmonary exacerbation episodes. Lung function measurements and sputum microbiological analyses were performed. In parallel, the inflammatory response and corticosteroid sensitivity of airway epithelial cells to Pseudomonas-derived exoproducts was investigated.We report that adult CF patients colonised with mucoid Pseudomonas aeruginosa have higher levels of baseline inflammation, more frequent exacerbations and worse lung function compared with patients colonised with nonmucoid P. aeruginosa. Moreover, mucoid P. aeruginosa activates NF-κB via Toll-like receptor (TLR) 2, which acts in an additive manner to TLR5 to drive inflammation in airway epithelial cells. Furthermore, TLR2-mediated intracellular signalling is more resistant to the anti-inflammatory effects of corticosteroid when compared with other TLR signalling pathways.Overall, these results suggest that airway inflammation triggered by mucoid P. aeruginosa is less responsive to the anti-inflammatory action of corticosteroids. Whether this translates into a diminished response of CF patients to corticosteroid therapy should be examined in future clinical studies.TLR2 activation by mucoid Pseudomonas increases corticosteroid-resistant inflammation in airway epithelial cells http://ow.ly/lR3d30bsRrr