| First Author | Lin X | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 33 | Pages | 11764-11775 |
| PubMed ID | 32587089 | Mgi Jnum | J:299146 |
| Mgi Id | MGI:6477885 | Doi | 10.1074/jbc.RA120.014298 |
| Citation | Lin X, et al. (2020) Ubiquitination of interleukin-1alpha is associated with increased pro-inflammatory polarization of murine macrophages deficient in the E3 ligase ITCH. J Biol Chem 295(33):11764-11775 |
| abstractText | Macrophages play critical roles in homeostasis and inflammation. Macrophage polarization to either a pro-inflammatory or anti-inflammatory status is controlled by activating inflammatory signaling pathways. Ubiquitination is a posttranslational modification that regulates these inflammatory signaling pathways. However, the influence of protein ubiquitination on macrophage polarization has not been well studied. We hypothesized that the ubiquitination status of key proteins in inflammatory pathways contributes to macrophage polarization, which is regulated by itchy E3 ubiquitin ligase (ITCH), a negative regulator of inflammation. Using ubiquitin proteomics, we found that ubiquitination profiles are different among polarized murine macrophage subsets. Interestingly, interleukin-1alpha (IL-1alpha), an important pro-inflammatory mediator, was specifically ubiquitinated in lipopolysaccharide-induced pro-inflammatory macrophages, which was enhanced in ITCH-deficient macrophages. The ITCH-deficient macrophages had increased levels of the mature form of IL-1alpha and exhibited pro-inflammatory polarization, and reduced deubiquitination of IL-1alpha protein. Finally, IL-1alpha neutralization attenuated pro-inflammatory polarization of the ITCH-deficient macrophages. In conclusion, ubiquitination of IL-1alpha is associated with increased pro-inflammatory polarization of macrophages deficient in the E3 ligase ITCH. |
