Granylocyte colony-stimulating factor attenuates LPS-stimulated IL-1β release via suppressed processing of proIL-1β, whereas TNF-α release is inhibited on the level of pro TNF-α formation

Eva Maria Boneberg, Thomas Hartung

Research output: Contribution to journalArticlepeer-review

Abstract

In the presence of granulocyte colony-stimulating factor (G-CSF), the release of IL-1β and TNF-α by LPS-stimulated human whole blood was suppressed. Via measurement of cytokine mRNA, inactive precursor and mature protein, we investigated whether this inhibition occurs at the transcriptional, translational or post-translational level of cytokine production. G-CSF inhibited IL-1β release, but the formation of proIL-1β was not attenuated, indicating that G-CSF interferes with the proteolytic processing of proIL-1β. Since the release of IL-1β in LPS-stimulated whole blood was blocked by the caspase-1 inhibitor YVAD-cmk, processing of proIL-1β appears to depend on caspase-1 activity. The conclusion that G-CSF inhibits caspase-1 activity was supported by the finding that the release of IL-18 was also inhibited by G-CSF, similar to IL-1β release. Intracellular caspase-1 activity in monocytes was measured by flow cytometry with the cell-permeable caspase substrate Asp2-rhodamine. In the presence of G-CSF the cleavage of this substrate was inhibited by more than 50%. G-CSF had no effect on LPS-induced doubling of caspase-1 mRNA, indicating that G-CSF affects caspase-1 activation and not its formation. For TNF-α another mechanism of G-CSF action was identified: TNF-α as well as proTNF-α formation were inhibited by G-CSF, but G-CSF had no influence on LPS-induced TNF-α mRNA level. We therefore suggest that G-CSF causes translational silencing of LPS-induced TNF-α mRNA.

Original languageEnglish (US)
Pages (from-to)1717-1725
Number of pages9
JournalEuropean Journal of Immunology
Volume32
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Blood
  • Growth factor
  • Immunomodulator
  • Inflammatory mediator
  • Monocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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