RT Journal Article SR Electronic T1 Nontypeable haemophilus influenzae (NTHi) leads to caspase-1-dependent upregulation of interleukin 1-beta (IL-1β) in respiratory cells and human lung tissue – A role of the “inflammasome” in respiratory tract infections JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP p2501 VO 38 IS Suppl 55 A1 Johannes Rotta detto Loria A1 Kristina Rohmann A1 Torsten Goldmann A1 Jan Rupp A1 Daniel Droemann A1 Klaus Dalhoff YR 2011 UL http://erj.ersjournals.com/content/38/Suppl_55/p2501.abstract AB The role of the inflammasome in pulmonary inflammation due to respiratory infections is still not well understood. As the inflammasome is a heterogeneous group of proteins, we focused on one obligatory component, caspase-1. We investigated if inhibition leads to a decrease of IL-1β after infection with NTHi and if it induces other proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and CXCL2.Murine alveolar macrophages (RAW 264.7) and human lung tissue were stimulated in-vitro with NTHi 106cfu/ml for 24-48h. A caspase-1 inhibitor (CI) was added 8h after infection. Supernatant and cells were collected for ELISA, PCR and Western Blot analysis.Cell and tissue culture experiments showed a significant induction of IL-1β-production after NTHi-in vitro-infection (RAW: Med 24h and 48h <15.6±0pg/ml vs. NTHi 24h 408±64pg/ml and NTHi 48h 717±72pg/ml, both n=6, p<0.01). Caspase-1 was activated 60min after infection. Inhibition of caspase-1 significantly decreases IL-1β levels after 24h (NTHi 24h 408±64pg/ml vs. NTHi+CI 24h 174±12pg/ml, n=6, p<0.01) and 48h of NTHi infection (NTHi 48h 717±72pg/ml vs. NTHi 48h 432±49pg/ml, n=6, p<0.01). PCR data confirmed the inhibitory effect. We did not observe significant changes in TNF-α and CXCL2 release after caspase-1 inhibition what means that these cytokines are not affected by inhibiting caspase-1.These results indicate that caspase-1-mediated IL-1β-upregulation is an important mechanism of NTHi-induced inflammation in pulmonary tissues and might be a central mediator in the pathogenesis of respiratory tract infections.