GM-CSF suppresses antioxidant signaling and drives IL-1β secretion through NRF2 downregulation

ABSTRACT: GM-CSF is a potent inflammatory cytokine regulating myeloid cell differentiation, hematopoiesis and various other functions. It is functionally associated with a number of inflammatory pathologies including rheumatoid arthritis and inflammatory bowel disease. GM-CSF has been found to promote NLRP3 dependent IL-1β secretion, which may have a significant role in driving inflammatory pathologies. However the molecular mechanisms remain unknown. Here we show that GM-CSF induces IL-1β secretion through a ROS dependent pathway. TNF is required for reactive oxygen species (ROS) generation that strikingly does not promote NLRP3 activation, but instead drives ubiquitylation of IL-1β, promoting its cleavage through basal NRLP3 activity. GM-CSF regulates this pathway through suppression of antioxidan

SUBMITTER: Ms. Sara Di Carlo 

PROVIDER: S-SCDT-EMBOR-2021-54226-T | biostudies-other |

REPOSITORIES: biostudies-other