Acute inflammation in response to both exogenous and endogenous danger signals can lead to the assembly of cytoplasmic inflammasomes that stimulate the activation of caspase-1. Subsequently, caspase-1 facilitates the maturation and release of cytokines and also, under some circumstances, the induction of cell death by pyroptosis. Using a mouse line lacking expression of NLRP1, we show that assembly of this inflammasome in cells is triggered by a toxin from Anthrax and that it initiates caspase-1 activation and release of IL-1β. Furthermore, NLRP1 inflammasome activation also leads to cell death, which escalates over three days following exposure to the toxin and culminates in acute lung injury and death of the mice. We show that these events are not dependent on production of IL-1β by the inflammasome but are dependent on caspase-1 expression. In contrast, MDP mediated inflammasome formation is not dependent on NLRP1, but NLRP3. Taken together, our findings show that assembly of the NLRP1 inflammasome is sufficient to initiate pyroptosis, which subsequently leads to a self-amplifying cascade of cell injury within the lung from which the lung cannot recover, eventually resulting in catastrophic consequences for the organism.

Locally crystallized PCN is prone to form *OCCHO groups rather than *CH2O groups, regulating the endoergic C–C coupling step to a simultaneous exoergic reaction and changing the reaction pathway towards CH3CHO (selectivity of 98.3%) instead of HCHO.

Background The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective To compare influenza-induced activation of inflammasome and innate immune signaling in human bronchial epithelial cells from asthmatics and non-asthmatics and investigate the role of caspase-1 in epithelial cell antiviral defense. Methods Differentiated primary human bronchial epithelial cells from asthmatics and non-asthmatics were infected with influenza A virus. An inflammasome-specific quantitative real-time polymerase chain reaction array was used to compare baseline and influenza-induced gene expression profiles. Cytokine secretion, innate immune gene expression, and viral replication were compared between human bronchial epithelial cells from asthmatics and non-asthmatics. Immunofluorescence microscopy was used to evaluate caspase-1 and PYCARD co-localization. Tracheal epithelial cells from caspase-1 deficient or wildtype mice were infected with influenza and assessed for antiviral gene expression and viral replication. Results Human bronchial epithelial cells from asthmatics had altered influenza-induced expression of inflammasome-related and innate immune signaling components, which correlated with enhanced production of interlukin-1β, interleukin-6, and tumor necrosis factor-α. Specifically, influenza-induced caspase-1 expression was enhanced and localization differed in human bronchial epithelial cells from asthmatics compared to non-asthmatics. Influenza-infected tracheal epithelial cells from caspase-1 deficient mice had reduced expression of antiviral genes and viral replication. Conclusion Caspase-1 plays an important role in the airway epithelial cell response to influenza infection, which is enhanced in asthmatics and may contribute to the enhanced influenza related pathogenesis observed in vivo.

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