Interleukin 1 is processed and released during apoptosis

Kristin A. Hogquist, Michelle A. Nett, Emil R. Unanue, David D. Chaplin

Research output: Contribution to journalArticlepeer-review

413 Scopus citations

Abstract

Interleukin (IL-) 1α and 1β are synthesized as 31- to 34-kDa pro molecules. They are released from monocytes and macrophages as proteolytically processed 17-kDa mature molecules that bind with high affinity to specific receptors on target cells. IL-1 is not released via the classic secretory pathway. The pro molecules are synthesized as cytosolic proteins without signal peptides. Although the proteases that convert the pro molecules to the mature forms are cytosolic enzymes, processed IL-1 is not detected associated with the cell but is found only in culture supernatants. We demonstrate here that release of IL-1 is efficiently induced by cell injury. When the injury causes cellular necrosis, IL-1α is released as a mixture of unprocessed and processed molecules but IL-1α is released exclusively as the biologically inactive pro form. In contrast, when cells undergo apoptosis, maturation of both IL-1α and IL-1β is efficient. When apoptosis is rapid, as in macrophages that are targets for allospecific cytotoxic T lymphocytes, processing is observed to occur intracellularly. These findings suggest that cell injury is an important physiologic stimulus for release of IL-1. The nature of the injury profoundly affects the forms of IL-1 that are released.

Original languageEnglish (US)
Pages (from-to)8485-8489
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number19
DOIs
StatePublished - Oct 1 1991

Keywords

  • ATP
  • Cell injury
  • Cytotoxic T lymphocyte
  • Necrosis

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