| First Author | Luheshi NM | Year | 2009 |
| Journal | Eur J Immunol | Volume | 39 |
| Issue | 11 | Pages | 2973-80 |
| PubMed ID | 19839011 | Mgi Jnum | J:154168 |
| Mgi Id | MGI:4367377 | Doi | 10.1002/eji.200939712 |
| Citation | Luheshi NM, et al. (2009) Nuclear retention of IL-1alpha by necrotic cells: A mechanism to dampen sterile inflammation. Eur J Immunol 39(11):2973-2980 |
| abstractText | 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-1alpha 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-1alpha is produced by microglia, the resident brain macrophages. We found that IL-1alpha is actively trafficked to the nuclei of microglia, and hence tested the hypothesis that trafficking of IL-1alpha 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-1alpha released significantly less IL-1alpha than microglia with predominantly cytosolic IL-1alpha. The remaining IL-1alpha was immobilized in the nuclei of the dead cells. Thus, nuclear retention of IL-1alpha may serve to limit inflammation following cell death. |
