• Authors: Baroja-Mazo, A., Compan, V., Martin-Sanchez, F., Tapia-Abellan, A., Couillin, I., Pelegrin, P.
  • Year: 2019
  • Journal: Sci Rep 9 5788
  • Applications: in vitro / Protein/Peptide/Antibody / PULSin
  • Cell types:
    1. Name: Mouse bone marrow-derived macrophages
      Description: Primary mouse bone marrow macrophages
      Known as: BMDM
    2. Name: THP-1
      Description: Human acute monocytic leukaemia cells
      Known as: THP1, THP 1




Unconventional protein secretion represents an important process of the inflammatory response. The release of the pro-inflammatory cytokine interleukin (IL)-1beta which burst during pyroptosis as a consequence of gasdermin D plasma membrane pore formation, can also occur through other unconventional secretion pathways dependent on caspase-1 activation. However, how caspase-1 mediates cytokine release independently of gasdermin D remains poorly understood. Here we show that following caspase-1 activation by different inflammasomes, caspase-1 cleaves early endosome autoantigen 1 (EEA1) protein at Asp(127/132). Caspase-1 activation also results in the release of the endosomal EEA1 protein in a gasdermin D-independent manner. EEA1 knock-down results in adecreased release of caspase-1 and IL-1beta, but the pyroptotic release of other inflammasome components and lactate dehydrogenase was not affected. This study shows how caspase-1 control the release of EEA1 and IL-1beta in a pyroptotic-independent manner.