| First Author | Lamacchia C | Year | 2013 |
| Journal | Cytokine | Volume | 63 |
| Issue | 2 | Pages | 135-44 |
| PubMed ID | 23684408 | Mgi Jnum | J:321471 |
| Mgi Id | MGI:6858429 | Doi | 10.1016/j.cyto.2013.04.010 |
| Citation | Lamacchia C, et al. (2013) Endogenous IL-1alpha is a chromatin-associated protein in mouse macrophages. Cytokine 63(2):135-44 |
| abstractText | The cytokine interleukin-1alpha (IL-1alpha) is synthesized as a 31kDa peptide that lacks a leader peptide and is not secreted by the conventional secretory pathway. A distinctive characteristic of pro-IL-1alpha is the presence of a nuclear localization sequence in its amino-terminal moiety that allows its translocation to the nucleus. However no nuclear function(s) of the endogenous pro-IL-1alpha has been reported to date. In the present study, we used murine macrophages that produce IL-1alpha in response to pro-inflammatory stimuli, to gain further insight into the biology of the endogenous IL-1alpha protein in innate immune cells. We show that endogenous IL-1alpha is essentially found as a chromatin-associated nuclear protein in LPS-stimulated macrophages. In contrast to IL-1beta, IL-1alpha was not released upon inflammasome activation unless significant cell damage occurred. IL-1beta mRNA and protein levels were specifically decreased in IL-1alpha deficient macrophages after LPS stimulation. However, overexpression of human pro-IL-1alpha did not rescue this defective IL-1beta production, suggesting that this finding might be related to the insertion of the targeting construct into the IL-1 locus, rather than to a specific nuclear function of pro-IL-1alpha. Finally, by using both genomic and proteomic approaches, we could not identify a nuclear function of IL-1alpha. Taken together, these observations suggest that in macrophages IL-1alpha primarily acts as an alarmin that is rapidly released upon cell damage to activate early mechanisms of host defense. |
