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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kostura, M. J. Chin, J. Cameron, P. Schmidt, J. A. Chartrain, N. A. Hillman, A. G. Tocci, M. J. Limjuco, G. |
| Description | Author Affiliation: Kostura MJ ( Department of Biochemical and Molecular Pathology, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.); |
| Abstract | Interleukin 1 (IL-1) is a lymphokine secreted by monocytes in response to a variety of inflammatory stimuli. IL-1 beta, the predominant form of IL-1 produced by human monocytes, is synthesized as an inactive precursor of 31 kDa and is cleaved at Asp116-Ala117 to yield a 17.5-kDa extracellular form. The exact cellular site of cleavage and mechanism of secretion is at present unknown. We have prepared cell-free postnuclear extracts from freshly isolated human monocytes as well as THP.1 cells, a human monocyte-like cell line, and various blood lymphocytes and fibroblast cell lines. Using pre-IL-1 beta synthesized by in vitro transcription and translation, we have shown that only extracts derived from human monocytes and THP.1 cells were capable of cleaving precursor IL-1 beta to authentic mature IL-1 beta. Subcellular fractionation of the extracts suggested that the processing activity is found in the cytosol of monocytes or monocyte-like cell lines. The cleavage product of this protease is identical to authentic IL-1 beta as shown by mobility on SDS/PAGE and amino acid sequence analysis of the [3H]leucine-labeled product. The cleavage product is also capable of binding to the IL-1 receptor found on fibroblast membranes. Finally, mutation of Asp116----Ala116 rendered the IL-1 beta precursor resistant to cleavage by the processing activity. We conclude that a protease activity found only in monocytes will specifically process IL-1 beta to an active form. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 14 |
| Volume Number | 86 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1989-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Interleukin-1 Genetics Metalloendopeptidases Blood Monocytes Enzymology Protein Precursors Caspase 1 Cell Line Cell-Free System Cells, Cultured Centrifugation, Density Gradient Isolation & Purification Mutation Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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