Research output: Contribution to journal › Article › peer-review
Expression dynamics of the REL, RELA, and IRF1 transcription factors in U937 macrophages after dioxin exposure. / Kashina, E. V.; Oshchepkov, D. Y.; Antontseva, E. V. et al.
In: Russian Journal of Genetics: Applied Research, Vol. 7, No. 5, 01.07.2017, p. 580-584.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Expression dynamics of the REL, RELA, and IRF1 transcription factors in U937 macrophages after dioxin exposure
AU - Kashina, E. V.
AU - Oshchepkov, D. Y.
AU - Antontseva, E. V.
AU - Shamanina, M. Y.
AU - Furman, D. P.
AU - Mordvinov, V. A.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is involved in a wide range of critical cellular events in response to endogenous signals or xenobiotics. 2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD) is one of the AhR ligands with the maximum affinity for AhR. TCDD is the most toxic among the dioxin xenobiotics and induces a wide range of biological responses, including immunotoxicity and cancer. The complex ligand:AhR:ARNT functions as a transcription factor, binding to the dioxin responsive element (DRE) sequences in the regulatory regions of target genes. Macrophages are key regulators of the innate immune response and being present in all body organs and tissues, they are one of the cell types that are the first to encounter xenobiotics; thus, the insight into the TCDD effect on macrophages is of paramount importance. Putative DREs are predicted using the SITECON software tool in the regulatory regions of the genes encoding transcription factors REL, RELA, and IRF1, expressed in macrophages. The nuclear extract and total RNA are isolated from the U937 macrophage-like cells exposed to 10 nM TCDD (or 0.1% DMSO as the control) for 1, 3, and 6 h. The binding of the TCDD:AhR:ARNT transcription complex from the nuclear extract with double-stranded oligonucleotides containing the putative DREs was studied by the EMSA. Quantitative real-time PCR demonstrates that the expression of these genes in the U937 macrophages increases in a statistically significant manner 1 h (the characteristic time of the maximal dioxin:AhR:ARNT translocation to the nucleus) after exposure to 10 nM TCDD. These results confirm the functional activity of the DREs residing in the IRF1, REL, and RELA regulatory regions via the AhR signaling pathway.
AB - The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is involved in a wide range of critical cellular events in response to endogenous signals or xenobiotics. 2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD) is one of the AhR ligands with the maximum affinity for AhR. TCDD is the most toxic among the dioxin xenobiotics and induces a wide range of biological responses, including immunotoxicity and cancer. The complex ligand:AhR:ARNT functions as a transcription factor, binding to the dioxin responsive element (DRE) sequences in the regulatory regions of target genes. Macrophages are key regulators of the innate immune response and being present in all body organs and tissues, they are one of the cell types that are the first to encounter xenobiotics; thus, the insight into the TCDD effect on macrophages is of paramount importance. Putative DREs are predicted using the SITECON software tool in the regulatory regions of the genes encoding transcription factors REL, RELA, and IRF1, expressed in macrophages. The nuclear extract and total RNA are isolated from the U937 macrophage-like cells exposed to 10 nM TCDD (or 0.1% DMSO as the control) for 1, 3, and 6 h. The binding of the TCDD:AhR:ARNT transcription complex from the nuclear extract with double-stranded oligonucleotides containing the putative DREs was studied by the EMSA. Quantitative real-time PCR demonstrates that the expression of these genes in the U937 macrophages increases in a statistically significant manner 1 h (the characteristic time of the maximal dioxin:AhR:ARNT translocation to the nucleus) after exposure to 10 nM TCDD. These results confirm the functional activity of the DREs residing in the IRF1, REL, and RELA regulatory regions via the AhR signaling pathway.
KW - AhR
KW - dioxin
KW - macrophage
KW - transcription factor IRF1
KW - transcription factor REL
KW - transcription factor RELA
UR - http://www.scopus.com/inward/record.url?scp=85028021804&partnerID=8YFLogxK
U2 - 10.1134/S2079059717050082
DO - 10.1134/S2079059717050082
M3 - Article
AN - SCOPUS:85028021804
VL - 7
SP - 580
EP - 584
JO - Russian Journal of Genetics: Applied Research
JF - Russian Journal of Genetics: Applied Research
SN - 2079-0597
IS - 5
ER -
ID: 9962586