Selenoproteins regulate macrophage invasiveness and extracellular matrix-related gene expression.
BACKGROUND
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 selenium-containing proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins is mediated by Sec tRNA([Ser]Sec).


RESULTS
To 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.


CONCLUSIONS
Selenium status may affect immune defense and tissue homeostasis through its effect on selenoprotein expression and the trafficking of tissue macrophages.
Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. carlsonb@mail.nih.gov
Bradley A
BA
Carlson
Min-Hyuk
MH
Yoo
Yasuyo
Y
Sano
Aniruddha
A
Sengupta
Jin Young
JY
Kim
Robert
R
Irons
Vadim N
VN
Gladyshev
Dolph L
DL
Hatfield
Jin Mo
JM
Park
D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D017453:Dermatitis, Irritant / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010703:Phorbol Esters / Q000008:administration & dosage; D012343:RNA, Transfer / Q000235:genetics; D051140:Selenoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015054:Zymosan / Q000008:administration & dosage
D016207:Cytokines; D016326:Extracellular Matrix Proteins; D008070:Lipopolysaccharides; D010703:Phorbol Esters; D051140:Selenoproteins; D015054:Zymosan; D012343:RNA, Transfer