| First Author | Nishina T | Year | 2012 |
| Journal | Sci Signal | Volume | 5 |
| Issue | 207 | Pages | ra5 |
| PubMed ID | 22253262 | Mgi Jnum | J:244813 |
| Mgi Id | MGI:5913592 | Doi | 10.1126/scisignal.2002056 |
| Citation | Nishina T, et al. (2012) Interleukin-11 links oxidative stress and compensatory proliferation. Sci Signal 5(207):ra5 |
| abstractText | Apoptotic cells can stimulate the compensatory proliferation of surrounding cells to maintain tissue homeostasis. Although oxidative stress is associated with apoptosis and necrosis, whether it contributes to compensatory proliferation is unknown. Here, we showed that interleukin-11 (IL-11), a member of the IL-6 family of proinflammatory cytokines, was produced by cells in an oxidative stress-dependent manner. IL-11 production depended on the activation in dying cells of extracellular signal-regulated kinase 2, which in turn caused the phosphorylation and accumulation of the transcription factor Fra-1 by preventing its proteasome-dependent degradation. Fra-1 was subsequently recruited to the Il11 promoter and activated gene transcription. Upon acute liver injury in mice, IL-11 was mainly produced by hepatocytes in response to reactive oxygen species that were presumably released from dying hepatocytes. IL-11 that was secreted by the dying cells then induced the phosphorylation of the transcription factor STAT3 in adjacent healthy hepatocytes, which resulted in their compensatory proliferation. Furthermore, an IL-11 receptor (IL-11R) agonist enhanced the proliferation of hepatocytes and ameliorated oxidative stress upon acetaminophen-induced liver injury. Conversely, the effects of acetaminophen were exacerbated in mice deficient in the IL-11R alpha subunit. Together, these results suggest that IL-11 provides a functional link between oxidative stress and compensatory proliferation. |
