Abstract
BackgroundSelenium, a micronutrient whose deficiency in diet causes immune dysfunction and inflammatory disorders, is thought to exert its physiological effects mostly in the form of selenium-containing proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins is mediated by Sec tRNA[Ser]Sec.ResultsTo define macrophage-specific selenoprotein functions, we generated mice with the Sec tRNA[Ser]Sec gene specifically deleted in myeloid cells. These mutant mice were devoid of the "selenoproteome" in macrophages, yet exhibited largely normal inflammatory responses. However, selenoprotein deficiency led to aberrant expression of extracellular matrix-related genes, and diminished migration of macrophages in a protein gel matrix.ConclusionSelenium status may affect immune defense and tissue homeostasis through its effect on selenoprotein expression and the trafficking of tissue macrophages.
Highlights
Selenium, a micronutrient whose deficiency in diet causes immune dysfunction and inflammatory disorders, is thought to exert its physiological effects mostly in the form of seleniumcontaining proteins
Compared to 3T3 fibroblasts, a nonmyeloid cell type that we used in parallel, macrophages expressed relatively high levels of genes encoding glutathione peroxidases 1 (GPx1), thioredoxin reductase 1 (TR1), the 15-kDa selenoprotein (Sep15), and selenoproteins P, R, K, and T (Figure 1A)
To compare selenoprotein gene expression in resting and activated macrophages, bone marrowderived macrophages (BMDMs) were subjected to RNA extraction with and without treatment with lipopolysaccharide (LPS), a toll-like receptor 4 (TLR4) agonist that induces potent inflammatory responses
Summary
A micronutrient whose deficiency in diet causes immune dysfunction and inflammatory disorders, is thought to exert its physiological effects mostly in the form of seleniumcontaining proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins is mediated by Sec tRNA[Ser]Sec. Macrophages, a class of myeloid leukocytes with phagocytic activity and inflammatory signaling properties, play a pivotal role in antimicrobial defense and tissue homeostasis [1,2,3]. Macrophages, a class of myeloid leukocytes with phagocytic activity and inflammatory signaling properties, play a pivotal role in antimicrobial defense and tissue homeostasis [1,2,3] These tissue-resident immune cells express receptors that detect the presence of signature molecules associated with microbial infection and tissue damage [4,5]. Uncontrolled macrophage recruitment and activation is associated with development of rheumatic, cardiovascular, metabolic, and neoplastic disorders
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.