PT - JOURNAL ARTICLE AU - Johannes Rotta detto Loria AU - Kristina Rohmann AU - Daniel Drömann AU - Jan Rupp AU - Torsten Goldmann AU - Klaus Dalhoff TI - <em>Nontypeable</em> haemophilus influenzae leads to activation of the NLRP3 inflammasome - A possible trigger of chronic bronchial inflammation in COPD DP - 2012 Sep 01 TA - European Respiratory Journal PG - P2513 VI - 40 IP - Suppl 56 4099 - http://erj.ersjournals.com/content/40/Suppl_56/P2513.short 4100 - http://erj.ersjournals.com/content/40/Suppl_56/P2513.full SO - Eur Respir J2012 Sep 01; 40 AB - The inflammasome is a cytosolic protein complex which is involved in a variety of inflammatory diseases. Since it represents a heterogeneous group of proteins, we elucidated which specific set of proteins is recruited after stimulation with nontypeable Haemophilus influenzae (NTHi). In view of the fact that IL-1β is a central early phase inflammatory cytokine, we investigated whether inflammasome inhibition affects other cytokines like IL-8 and TNF-α.Murine macrophages and human lung tissue were stimulated with NTHi 106cfu/ml for 24-48h. To assess the relevance of the inflammasome for the inflammatory response, a caspase-1 inhibitor (CI) was added after in-vitro infection. The inflammatory response was measured by cytokine ELISA and Western Blot.Western Blot analysis showed the activation of caspase-1 after NTHi infection and moreover the expression of the NOD-like receptors NOD1 and NLRP3. In cell culture and human lung tissue experiments IL-1β production was significantly induced (RAW: control 24h beneath lowest standard vs. NTHi 24h 408±64pg/ml, n=6, p&lt;0.01). The inhibition of caspase-1 led to a significant reduction of IL-1β levels and also to a decrease of IL-8 and TNF-α production (IL-1β: NTHi 24h 408±64pg/ml vs. NTHi+CI 24h 174±12pg/ml, n=6, p&lt;0.01).For the first time we demonstrate the participation of the NRLP3-inflammasome in NTHi-induced inflammation in pulmonary cells and tissues. Our findings concerning caspase-1 mediated IL-1β-upregulation emphasize the role of the inflammasome in respiratory tract infections. These results may provide new insights into the pathogenesis of persistent airway inflammation in COPD.