A novel secretory pathway for interleukin-1β, a protein lacking a signal sequence

A. Rubartelli, F. Cozzolino, M. Talio, R. Sitia

Research output: Contribution to journalArticle

Abstract

Interleukin 1 (IL-1) is a major soluble mediator of inflammation. Two human IL-1 genes, α and β, have been isolated, which encode polypeptides with only 20-30% amino acid sequence homology. Unlike most secreted proteins, the two cytokines do not have a signal sequence, an unexpected finding in view of their biological role. Here we show that IL-1β is actively secreted by activated human monocytes via a pathway of secretion different from the classical endoplasmic reticulum - Golgi route. Drugs which block the intracellular transport of IL-6, of tumour necrosis factor α and of other secretory proteins do not inhibit secretion of IL-1β. Secretion of IL-1β is blocked by methylamine, low temperature or serum free medium, and is increased by raising the culture temperature to 42°C or by the presence of calcium ionophores, brefeldin A, monensin, dinitrophenol or carbonyl cyanide chlorophenylhydrazone. IL-1β is contained in part within intracellular vesicles which protect it from protease digestion. In U937 cells large amounts of IL-1β are made but none is secreted. In these cells IL-1β is not found in the vesicular fraction, and all the protein is accessible to protease digestion. This suggests that intracellular vesicles that contain IL-1β are part of the protein secretory pathway. We conclude that IL-1β is released by activated monocytes via a novel mechanism of secretion which may involve translocation of intracellular membranes and is increased by stress conditions.

Original languageEnglish
Pages (from-to)1503-1510
Number of pages8
JournalEMBO Journal
Volume9
Issue number5
Publication statusPublished - 1990

Keywords

  • endoplasmic reticulum
  • interleukin-1
  • secretion
  • signal sequence
  • translocation

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

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