Details

Autor(en) / Beteiligte

• Kostura, Matthew J.
• Tocci, Michael J.
• Limjuco, Guadalupe
• Chin, Jayne
• Cameron, Patricia
• Hillman, Andrew G.
• Chartrain, Nicole A.
• Schmidt, John A.

Titel

Identification of a Monocyte Specific Pre-Interleukin 1β Convertase Activity

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1989-07, Vol.86 (14), p.5227-5231

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1989

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Interleukin 1 (IL-1) is a lymphokine secreted by monocytes in response to a variety of inflammatory stimuli. IL-1β , 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-1β 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-1β to authentic mature IL-1β . 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-1β 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-1β precursor resistant to cleavage by the processing activity. We conclude that a protease activity found only in monocytes will specifically process IL-1β to an active form.