The role of selenoproteins in resolution of inflammation

Bastihalli T. Diwakar, Emily R. Finch, Chang Liao, Ashley E. Shay, K. Sandeep Prabhu

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

Abstract

Inflammation is an evolutionarily conserved physiological response mounted with an intention to resolve the insult inflicted on the biological system. This process is extremely well orchestrated, where many cells, including macrophages, play key roles in facilitating discreet steps leading to the successful resolution and wound healing. As a result of oxidative stress during the initial phase of inflammation, cellular redox homeostasis holds utmost importance in shaping and dictating the cellular response, where selenoproteins play a critical role. Our studies in mice that lack macrophage expression of selenoproteins, via the deletion of Trsp, have demonstrated selenoprotein expression to be key in their polarization from a pro-inflammatory cell type towards an anti-inflammatory phenotype, which aids in resolution of inflammation and wound healing. Such a transition is accompanied by changes in cellular metabolism, particularly that of arachidonic acid, which leads to the formation of many bioactive oxylipids, including cyclopentenone prostaglandins (CyPGs). These endogenous metabolites differentially modulate signaling cascades and transcription factors to effect the switch in macrophage polarization. The ramifications of selenoprotein-dependent macrophage polarization in the resolution of inflammation in rodent models involving gut inflammation by chemical injury and parasitic infections are discussed here. In addition, the anti-carcinogenic role of macrophage-derived CyPG, produced in a selenoprotein-dependent manner, to impact the viability of cancer stem cells in hematologic malignancies will be discussed. Finally, we describe a new role for selenoproteins in the tissue microenvironment in shaping efficient stress erythropoiesis that is critical to resolve anemia that follows inflammation.

Original languageEnglish (US)
Title of host publicationSelenium
Subtitle of host publicationIts Molecular Biology and Role in Human Health, Fourth Edition
PublisherSpringer International Publishing
Pages499-510
Number of pages12
ISBN (Electronic)9783319412832
ISBN (Print)9783319412818
DOIs
StatePublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Diwakar, B. T., Finch, E. R., Liao, C., Shay, A. E., & Prabhu, K. S. (2016). The role of selenoproteins in resolution of inflammation. In Selenium: Its Molecular Biology and Role in Human Health, Fourth Edition (pp. 499-510). Springer International Publishing. https://doi.org/10.1007/978-3-319-41283-2_42