NLRP3 Inflammasome Activation Leading to IL-1 – IL-17 Dependent Lung Inflammation and Fibrosis

Title:NLRP3 Inflammasome Activation Leading to IL-1 – IL-17 Dependent Lung Inflammation and Fibrosis

Volume: 10 Issue: 1

Author(s): 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 Ryffel

Affiliation:

Keywords: Asthma, ATP, bleomycin, cigarette smoke, COPD, IL-1, IL-17, NLRP3 inflammasome, ozone, Th17 cells, uric acid.

Abstract: Chronic 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.

Cite this article as:

Togbe Dieudonnee, Besnard Anne-Gaelle, Madouri Fahima, Couillin Isabelle, Gombault Aurelie, Baron Ludivine, Froux Nathalie, Maillard Aurelie, Erard Francois, Snick Van Jacques, Uyttenhove Catherine, Quesniaux F. Valerie and Ryffel Bernhard, NLRP3 Inflammasome Activation Leading to IL-1 – IL-17 Dependent Lung Inflammation and Fibrosis, Current Respiratory Medicine Reviews 2014; 10 (1) . https://dx.doi.org/10.2174/1573398X10666140617001526