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 journalArticle

Abstract

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
Volume266
Issue number19
StatePublished - 1991
Externally publishedYes

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Calpain
Interleukins
Interleukin-1
Peptide Hydrolases
Macrophages
Processing
Calcium
Cells
Cell Line
Fibroblasts
Foreskin
Thymoma
Lymphoma, Large B-Cell, Diffuse
Monocytes
Monoclonal Antibodies
Molecular mass
Cell culture
Blood
interleukin 1 precursor
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Involvement of a calpain-like protease in the processing of the murine interleukin la precursor. / Carruth, Lucy M.; Demczuk, Stephen; Mizel, Steven B.

In: Journal of Biological Chemistry, Vol. 266, No. 19, 1991, p. 12162-12167.

Research output: Contribution to journalArticle

Carruth, Lucy M. ; Demczuk, Stephen ; Mizel, Steven B. / Involvement of a calpain-like protease in the processing of the murine interleukin la precursor. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 19. pp. 12162-12167.
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