Role of NADPH oxidase-derived reactive oxygen species in human neutrophil IL-1 beta secretion

GABELLONI ML; SABBIONE F; JANCIC C; KEITELMAN I; IULA L; OLEASTRO M; GEFFNER JR; TREVANI AS

Milán

Conferencia; 15th International Congress of Immunology; 2013

International Union of Immunological Societies

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. 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 reactive oxygenspecies (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
secretion, a role never previously described. The complex ROS-mediated regulation of neutrophil IL-1
secretion might constitute a physiological mechanism to control IL-1
-dependent inflammatory processes where neutrophils play a crucial role.