Source: Annual Congress 2012 - Prognostic indices in respiratory infections
Disease area: Airway diseases

Abstract

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<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<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.

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J. Rotta detto Loria, K. Rohmann, D. Drömann, J. Rupp, T. Goldmann, K. Dalhoff (Borstel, Germany). Nontypeable haemophilus influenzae leads to activation of the NLRP3 inflammasome – A possible trigger of chronic bronchial inflammation in COPD. Eur Respir J 2012; 40: Suppl. 56, 2513

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