Activation of the selenoprotein SEPS1 gene expression by pro-inflammatory cytokines in HepG2 cells.
SEPS1 (also called selenoprotein S, SelS) plays an important role in the production of inflammatory cytokines and its expression is activated by endoplasmic reticulum (ER) stress. In this report, we have identified two binding sites for the nuclear factor kappa B in the human SEPS1 promoter. SEPS1 gene expression, protein levels and promoter activity were all increased 2-3-fold by TNF-alpha and IL-1beta in HepG2 cells. We have also confirmed that the previously proposed ER stress response element GGATTTCTCCCCCGCCACG in the SEPS1 proximate promoter is fully functional and responsive to ER stress. However, concurrent treatment of HepG2 cells with IL-1beta and ER stress produced no additive effect on SEPS1 gene expression. We conclude that SEPS1 is a new target gene of NF-kappaB. Together with our previous findings that SEPS1 may regulate cytokine production in macrophage cells, we propose a regulatory loop between cytokines and SEPS1 that plays a key role in control of the inflammatory response.
Gao
Yuan
Y
Metabolic Research Unit, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia. yuan.gao@csiro.au
Hannan
Nicholas R F
NR
Wanyonyi
Stephen
S
Konstantopolous
Nicky
N
Pagnon
Joanne
J
Feng
Helen C
HC
Jowett
Jeremy B M
JB
Kim
Kee-Hong
KH
Walder
Ken
K
Collier
Greg R
GR
D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051140:Selenoproteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D008565:Membrane Proteins; D016328:NF-kappa B; C487710:SELENOS protein, human; D051140:Selenoproteins; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose