Involvement of a calpain-like protease in the processing of the murine interleukin la precursor

Lucy M. Carruth, Stephen Demczuk, Steven B. Mizel

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Interleukin (IL) la is synthesized as a 33-kDa precursor that is enzymatically cleaved to the 15-17-kDa forms that are found in the culture supernatants of activated macrophages. We have explored the possibility that calcium might enhance IL-1 processing and secretion via the stimulation of a calcium-dependent protease. We have found that lysates prepared from human peripheral blood monocytes, the human histiocytic lymphoma cell line U937, and the murine macrophage cell line P388D1 contain a calcium-dependent IL-1α processing activity that cleaves the IL-1α precursor to its mature form. Although NIH 3T3 mouse fibroblast cell lysates also contain IL-1 processing activity, lysates from the murine thymoma EL-4, the human epidermoid cell line HEp-2, and the human foreskin fibroblast line FS-4 lack this activity. IL-1 processing activity is inhibited by leupeptin and exhibits a molecular mass of 80-110 kDa. The processing activity is also inhibited by a monoclonal antibody directed against calpain type I. These results indicate that the processing of the IL-1α precursor is mediated, at least in part, by a member of the calpain family of proteases. Mixing experiments revealed that lysates from EL-4 or HEp-2 cells contain an inhibitor(s) of the calpain-like protease in macrophage extracts. It is, therefore, likely that many non-macrophage cell types are unable to process the IL-1α precursor because the calpain present in these cells is only weakly active due to the presence of a specific inhibitor(s) such as calpastatin.

Original languageEnglish (US)
Pages (from-to)12162-12167
Number of pages6
JournalJournal of Biological Chemistry
Issue number19
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Involvement of a calpain-like protease in the processing of the murine interleukin la precursor'. Together they form a unique fingerprint.

Cite this