Early endosome autoantigen 1 regulates IL-1β release upon caspase-1 activation independently of gasdermin D membrane permeabilization

Sci Rep. 2019 Apr 8;9(1):5788. doi: 10.1038/s41598-019-42298-4.

Abstract

Unconventional protein secretion represents an important process of the inflammatory response. The release of the pro-inflammatory cytokine interleukin (IL)-1β 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 Asp127/132. 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-1β, 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-1β in a pyroptotic-independent manner.

MeSH terms

  • Animals
  • Caspase 1 / metabolism*
  • Cells, Cultured
  • Endosomes / metabolism
  • HEK293 Cells
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Phosphate-Binding Proteins / metabolism*
  • Pyroptosis
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*

Substances

  • Gsdmd protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • Phosphate-Binding Proteins
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • Caspase 1