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 language | English (US) |
|---|---|
| Pages (from-to) | 1717-1725 |
| Number of pages | 9 |
| Journal | European Journal of Immunology |
| Volume | 32 |
| Issue number | 6 |
| DOIs | |
| State | Published - 2002 |
| Externally published | Yes |
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Keywords
- Blood
- Growth factor
- Immunomodulator
- Inflammatory mediator
- Monocyte
ASJC Scopus subject areas
- Immunology
Cite this
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. / Boneberg, Eva Maria; Hartung, Thomas.
In: European Journal of Immunology, Vol. 32, No. 6, 2002, p. 1717-1725.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Boneberg, Eva Maria
AU - Hartung, Thomas
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Blood
KW - Growth factor
KW - Immunomodulator
KW - Inflammatory mediator
KW - Monocyte
UR - http://www.scopus.com/inward/record.url?scp=0035983755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035983755&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(200206)32:6<1717::AID-IMMU1717>3.0.CO;2-N
DO - 10.1002/1521-4141(200206)32:6<1717::AID-IMMU1717>3.0.CO;2-N
M3 - Article
C2 - 12115655
AN - SCOPUS:0035983755
VL - 32
SP - 1717
EP - 1725
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 6
ER -