Reactive oxygen species are involved in the secretion of IL-1β but not in inflammasome activation in human neutrophils.

TREVANI AS

Simposio; Simposio sobre Inflamación - LXI Reunión annual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología

Neutrophils are essential players in acute inflammatory responses. Upon stimulation, neutrophils activate NADPH oxidase, generating an array of reactive oxygen species (ROS). Interleukin-1 (IL-1) is a major pro-inflammatory cytokine synthesized in the cytoplasm as a precursor that has to be proteolytically processed to become biologically active. The aim of our study was to determine the mechanisms involved in IL-1 processing and secretion by human neutrophil. We determined that in response to LPS and LPS plus ATP, human neutrophil IL-1 processing is dependent on caspase-1 and on elastase and/or proteinase-3. The role of ROS in IL-1 processing remains still controversial and has not been studied in neutrophils. We found that upon stimulation, NADPH oxidase-deficient neutrophils activated caspase-1 and did not exhibit differences in NALP3 expression as compared to healthy neutrophils, indicating that ROS are neither required for inflammasome activation nor for its priming, as has been reported in macrophages. Strikingly, ROS exerted opposite effects on the processing and secretion of IL-1; whereas ROS negatively controlled caspase-1 activity, as reported in mononuclear phagocytes, they were found necessary for IL-1 exportation, a role never previously described. The release of IL-1 does not follow the conventional ER-Golgi route of secretion and the mechanisms for its exportation have proven to be elusive. We will also discuss our recent data shedding light to the possible mechanism involved in IL-1β exportation in human neutrophils.