Inflammasome Activity in Non-Microbial Lung Inflammation

Abstract

The understanding of interleukin-1 (IL-1) family cytokines in inflammatory disease has rapidly developed, due in part to the discovery and characterization of inflammasomes, which are multi-subunit intracellular protein scaffolds principally enabling recognition of a myriad of cellular stimuli, leading to the activation of caspase-1 and the processing of IL-1β and IL-18. Studies continue to elucidate the role of inflammasomes in immune responses induced by both microbes and environmental factors. This review focuses on the current understanding of inflammasome activity in the lung, with particular focus on the non-microbial instigators of inflammasome activation, including inhaled antigens, oxidants, cigarette smoke, diesel exhaust particles, mineral fibers, and engineered nanomaterials, as well as exposure to trauma and pre-existing inflammatory conditions such as metabolic syndrome. Inflammasome activity in these sterile inflammatory states contribute to diseases including asthma, chronic obstructive disease, acute lung injury, ventilator-induced lung injury, pulmonary fibrosis, and lung cancer.

Keywords: IL-1; IL-18; inflammasome; inflammation; lung.

Figure 1

Differing structures of the inflammasomes implicated in lung disease

Figure 2

Pulmonary diseases in which inflammasome activation is involved, either through the production of caspase-1-regulated cytokines (IL-1β or IL-18) and/ or IL-17. COPD, chronic obstructive pulmonary disease.