Nuclear retention of IL-1 alpha by necrotic cells: a mechanism to dampen sterile inflammation.

Abstract

Sterile inflammation is a host response to tissue injury that is mediated by damage-associated molecular patterns released from dead cells. Sterile inflammation worsens damage in a number of injury paradigms. The pro-inflammatory cytokine IL-1 alpha is reported to be a damage-associated molecular pattern released from dead cells, and it is known to exacerbate brain injury caused by stroke. In the brain, IL-1 alpha is produced by microglia, the resident brain macrophages. We found that IL-1 alpha is actively trafficked to the nuclei of microglia, and hence tested the hypothesis that trafficking of IL-1 alpha to the nucleus would inhibit its release following necrotic cell death, limiting sterile inflammation. Microglia subjected to oxygen-glucose deprivation died via necrosis. Under these conditions, microglia expressing nuclear IL-1 alpha released significantly less IL-1 alpha than microglia with predominantly cytosolic IL-1 alpha. The remaining IL-1 alpha was immobilized in the nuclei of the dead cells. Thus, nuclear retention of IL-1 alpha may serve to limit inflammation following cell death.

• Authors: Nadia M Luheshi, Barry W McColl, David Brough
• Journal: European journal of immunology (Eur J Immunol) Vol. 39 Issue 11 Pg. 2973-80 (Nov 2009) ISSN: 1521-4141 [Electronic] Germany
• PMID: 19839011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1alpha

Topics

• Animals
• Cell Nucleus (metabolism)
• Humans
• Inflammation (metabolism)
• Interleukin-1alpha (metabolism)
• Microglia (metabolism)
• Necrosis (metabolism)
• Protein Transport (physiology)