NLRP3 Inflammasome Activation Leading to IL-1 – IL-17 Dependent Lung Inflammation and Fibrosis
Dieudonnee Togbe, Anne-Gaelle Besnard, Fahima Madouri, Isabelle Couillin, Aurelie Gombault, Ludivine Baron, Nathalie Froux, Aurelie Maillard, Francois Erard, Jacques Van Snick, Catherine Uyttenhove, Valerie F. Quesniaux and Bernhard RyffelAffiliation:
CNRS UMR7355, 45071 Orleans, France.
AbstractChronic bronchitis, pulmonary fibrosis, emphysema and allergic asthma are significant human health issues due to exposure to environmental pollutants, chemical irritants, cigarette smoke (CS) and allergens. Activation of the NLRP3 inflammasome with the release of active IL-1β is central to develop inflammatory lung pathology. We demonstrated that CS, microparticle (MP), bleomycin or allergens provoke the release of danger signals such as ATP and/or uric acid that activate the NLRP3 inflammasome. Activated NLPR3 recruits the adaptor protein ASC and activates caspase-1 with the release of mature IL-1β. IL-1β is a critical mediator of inflammation inducing IL-6, IL-23 as well as chemokines, which mobilize neutrophils and enhance the recruitment of Th17 cells in the lung with the production of IL- 17. Here, we review our experimental investigations that uncovered danger signals activating the NLRP3 inflammasome leading to IL-1 - IL-17 dependent lung inflammation, fibrosis and emphysema. The inflammasomes, IL-1β and IL-17 are critical in injury induced inflammatory lung pathology and represent therapeutic targets for future medicines.
Asthma, ATP, bleomycin, cigarette smoke, COPD, IL-1, IL-17, NLRP3 inflammasome, ozone, Th17 cells, uric acid.
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