Limits...
Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.

Tsuji PA, Carlson BA, Anderson CB, Seifried HE, Hatfield DL, Howard MT - Nutrients (2015)

Bottom Line: Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ.Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver.These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Towson University, Towson, MD, 21252, USA. ptsuji@towson.edu.

ABSTRACT
Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

No MeSH data available.


Related in: MedlinePlus

RNA-Seq and ribosome profiling of selenoprotein mRNAs. (A) and (B) show conceptual illustrations of RNA-Seq and ribosome profiling experiments, respectively. A representative selenoprotein mRNA is shown with the position of the UGA-Sec codon indicated by the vertical red bar. Randomly sheared (A) or ribosome protected (B) mRNA fragments are shown in dark or light grey to indicate whether they are positioned 5′ or 3′ of the UGA-Sec codon. (C) The histogram shows the fold-change in liver sequence reads per kilobase per million mapped reads (RPKM) in mice fed diets supplemented with 0.1 ppm Se (0.1 Se) relative to those fed unsupplemented diets (0 ppm Se). Dashed line across the histogram indicates a fold change value of 1 (no difference). (D–F) Same as in (C) for liver ribosome protected fragments, Liver qPCR and lung qPCR, respectively, with the exception that in (D) the RPKM values were determined only for the portion of the selenoprotein mRNA located 3′ of the UGA-Sec codon. Standard deviations were calculated by the Propagation of Error method.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4555136&req=5

nutrients-07-05297-f001: RNA-Seq and ribosome profiling of selenoprotein mRNAs. (A) and (B) show conceptual illustrations of RNA-Seq and ribosome profiling experiments, respectively. A representative selenoprotein mRNA is shown with the position of the UGA-Sec codon indicated by the vertical red bar. Randomly sheared (A) or ribosome protected (B) mRNA fragments are shown in dark or light grey to indicate whether they are positioned 5′ or 3′ of the UGA-Sec codon. (C) The histogram shows the fold-change in liver sequence reads per kilobase per million mapped reads (RPKM) in mice fed diets supplemented with 0.1 ppm Se (0.1 Se) relative to those fed unsupplemented diets (0 ppm Se). Dashed line across the histogram indicates a fold change value of 1 (no difference). (D–F) Same as in (C) for liver ribosome protected fragments, Liver qPCR and lung qPCR, respectively, with the exception that in (D) the RPKM values were determined only for the portion of the selenoprotein mRNA located 3′ of the UGA-Sec codon. Standard deviations were calculated by the Propagation of Error method.

Mentions: We have applied complimentary genome-wide methods, RNA-Seq and ribosome profiling as shown schematically in Figure 1A,B, respectively, and microarrays (see below), as well as qPCR to determine changes in gene expression and translational activity in liver and lung tissues of mice fed Se-deficient or Se-adequate diets. Liver was selected, as it is where Se is processed and converted into other forms appropriate for delivery through the circulatory system to other tissues, or for excretion [47]. Delivery of Se to other tissues is primarily mediated by uptake from the blood stream of liver-produced Sepp1, which contains up to 10 Se atoms in the form of Sec residues. Lung was selected as a second tissue, because selenoprotein expression in this tissue is strongly affected by Se dietary intake, and due to the fact that Se status has been proposed as a risk factor and modulation of intake as a potential preventative for a number of lung disorders with involvement of oxidative stress and inflammation [48,49,50,51].


Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice.

Tsuji PA, Carlson BA, Anderson CB, Seifried HE, Hatfield DL, Howard MT - Nutrients (2015)

RNA-Seq and ribosome profiling of selenoprotein mRNAs. (A) and (B) show conceptual illustrations of RNA-Seq and ribosome profiling experiments, respectively. A representative selenoprotein mRNA is shown with the position of the UGA-Sec codon indicated by the vertical red bar. Randomly sheared (A) or ribosome protected (B) mRNA fragments are shown in dark or light grey to indicate whether they are positioned 5′ or 3′ of the UGA-Sec codon. (C) The histogram shows the fold-change in liver sequence reads per kilobase per million mapped reads (RPKM) in mice fed diets supplemented with 0.1 ppm Se (0.1 Se) relative to those fed unsupplemented diets (0 ppm Se). Dashed line across the histogram indicates a fold change value of 1 (no difference). (D–F) Same as in (C) for liver ribosome protected fragments, Liver qPCR and lung qPCR, respectively, with the exception that in (D) the RPKM values were determined only for the portion of the selenoprotein mRNA located 3′ of the UGA-Sec codon. Standard deviations were calculated by the Propagation of Error method.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555136&req=5

nutrients-07-05297-f001: RNA-Seq and ribosome profiling of selenoprotein mRNAs. (A) and (B) show conceptual illustrations of RNA-Seq and ribosome profiling experiments, respectively. A representative selenoprotein mRNA is shown with the position of the UGA-Sec codon indicated by the vertical red bar. Randomly sheared (A) or ribosome protected (B) mRNA fragments are shown in dark or light grey to indicate whether they are positioned 5′ or 3′ of the UGA-Sec codon. (C) The histogram shows the fold-change in liver sequence reads per kilobase per million mapped reads (RPKM) in mice fed diets supplemented with 0.1 ppm Se (0.1 Se) relative to those fed unsupplemented diets (0 ppm Se). Dashed line across the histogram indicates a fold change value of 1 (no difference). (D–F) Same as in (C) for liver ribosome protected fragments, Liver qPCR and lung qPCR, respectively, with the exception that in (D) the RPKM values were determined only for the portion of the selenoprotein mRNA located 3′ of the UGA-Sec codon. Standard deviations were calculated by the Propagation of Error method.
Mentions: We have applied complimentary genome-wide methods, RNA-Seq and ribosome profiling as shown schematically in Figure 1A,B, respectively, and microarrays (see below), as well as qPCR to determine changes in gene expression and translational activity in liver and lung tissues of mice fed Se-deficient or Se-adequate diets. Liver was selected, as it is where Se is processed and converted into other forms appropriate for delivery through the circulatory system to other tissues, or for excretion [47]. Delivery of Se to other tissues is primarily mediated by uptake from the blood stream of liver-produced Sepp1, which contains up to 10 Se atoms in the form of Sec residues. Lung was selected as a second tissue, because selenoprotein expression in this tissue is strongly affected by Se dietary intake, and due to the fact that Se status has been proposed as a risk factor and modulation of intake as a potential preventative for a number of lung disorders with involvement of oxidative stress and inflammation [48,49,50,51].

Bottom Line: Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ.Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver.These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Towson University, Towson, MD, 21252, USA. ptsuji@towson.edu.

ABSTRACT
Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

No MeSH data available.


Related in: MedlinePlus