0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Ubiquitination of interleukin-1α is associated with increased pro-inflammatory polarization of murine macrophages deficient in the E3 ligase ITCH.

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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-1α (IL-1α), 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-1α and exhibited pro-inflammatory polarization, and reduced deubiquitination of IL-1α protein. Finally, IL-1α neutralization attenuated pro-inflammatory polarization of the ITCH-deficient macrophages. In conclusion, ubiquitination of IL-1α is associated with increased pro-inflammatory polarization of macrophages deficient in the E3 ligase ITCH.

          Related collections

          Author and article information

          Journal
          J Biol Chem
          The Journal of biological chemistry
          American Society for Biochemistry & Molecular Biology (ASBMB)
          1083-351X
          0021-9258
          August 14 2020
          : 295
          : 33
          Affiliations
          [1 ] Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA.
          [2 ] Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA.
          [3 ] Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA Lianping_xing@urmc.rochester.edu.
          Article
          S0021-9258(17)48474-2
          10.1074/jbc.RA120.014298
          7450106
          32587089
          261ceb3f-ca9d-4180-abe9-73e2167f849c
          © 2020 Lin et al.

          IL-1α,Interleukin-1α,Itch,deubiquitination,deubiquitylation (deubiquitination),inflammation,innate immunity,interleukin 1 (IL-1),itchy E3 ubiquitin protein ligase (ITCH),macrophage,macrophage polarization,posttranslational modification,proteomics,ubiquitination,ubiquitylation (ubiquitination)

          Comments

          Comment on this article