Table 2.
Intranuclear actions of IL-1α
| Cell type | IL-1α isoform | Intranuclear effect |
Evidence that effect is intranuclear |
References | ||||
|---|---|---|---|---|---|---|---|---|
| IL-1RA | neutralizing Ig | Exog. IL-1α | Expr. mature IL-1α | NLS mutation | ||||
| Intranuclear IL-1α effects on proliferation/cell death | ||||||||
| Endothelial cell line | pro-IL-1α | Inhibits proliferation | ✓ | ✗ | ✗ | ✓ | ✗ | Maier et al. (1994) |
| SaOS-2 | pro-IL-1α | Inhibits proliferation | ✓ | ✗ | ✓ | ✗ | ✗ | Palmer et al. (2005) |
| HEK-293, cancer cells | ppIL-1α | Induces apoptosis | ✗ | ✗ | ✗ | ✗ | ✓ | Pollock et al. (2003) |
| SSc and normal fibroblasts | pro-IL-1α | Enhances proliferation | ✓ | ✓ | ✓ | ✗ | ✗ | Kawaguchi et al. (2004) |
| Perivascular mesangial cells | ppIL-1α pro-IL-1α | Causes malignant transformation | ✗ | ✗ | ✗ | ✗ | ✓ | Stevenson et al. (1997) |
| Vascular smooth muscle cells | pro-IL-1α ppIL-1α Mature IL-1α | No effect of intranuclear IL-1α on proliferation | N/A | N/A | N/A | N/A | N/A | Beasley and Cooper (1999) |
| Intranuclear IL-1α effects on gene expression | ||||||||
| Endothelial cell line | pro-IL-1α | Induces PAI-1 and collagenase expression | ✓ | ✗ | ✗ | ✓ | ✗ | Maier et al. (1994) |
| NIH-3T3, COS-7, endothelial cell line | pro-IL-1α ppIL-1α | Induces IL-6, IL-8 and endogenous IL-1α expression Enhances IFNγ or TNFα induction of MIP-2 | ✓ | ✗ | ✗ | ✓ | ✗ | Werman et al. (2004) |
| HeLa, macrophages, HEK-293 | pro-IL-1α | Induces IL-8 expression | ✓ | ✓ | ✗ | ✗ | ✗ | Cheng et al. (2008) |
| SSc and normal fibroblasts | pro-IL-1α | Induces IL-6 and procollagen expression | ✓ | ✓ | ✓ | ✗ | ✗ | Kawaguchi et al. (2004) |
| Intranuclear IL-1α effects on cell migration | ||||||||
| Endothelial cell line | pro-IL-1α | Inhibits migration | ✓ | ✗ | ✗ | ✗ | ✓ | McMahon et al. (1997) |
| Endothelial cell line | pro-IL-1α ppIL-1α | Promotes migration | ✗ | ✗ | ✓ | ✓ | ✗ | Merhi-Soussi et al. (2005) |
Evidence that IL-1α effects described involve intranuclear IL-1α. IL-1RA: cell incubation with IL-1RA does not block effect. Exog. IL-1α: application of exogenous IL-1α to cells does not reproduce effect. Neutralizing Ig: incubation of cells with IL-1α-neutralizing antibody does not block effect. Expr. mature IL-1α: expression of mature IL-1α (lacking the NLS) does not reproduce effect. NLS mutation: mutation of IL-1α NLS blocks the effect.
COS-7, african green monkey kidney fibroblast cell line; HEK-293, human embryonic kidney cell line; HeLa, human cervical epithelial cell line; IFNγ, interferon-γ; IL-1, interleukin-1; IL-1RA, IL-1 receptor antagonist; MIP-2, macrophage inhibitory protein-2; N/A, not applicable, as no intranuclear IL-1α effect observed; NIH-3T3, murine fibroblast cell line; NLS, nuclear localization sequence; PAI-1, plasminogen activator inhibitor-1; ppIL-1α, IL-1α pro-piece; SaOS-2, human osteosarcoma cell line; SSc, systemic sclerosis; TNFα, tumour necrosis factor α.