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.
Metabolic Research Unit, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia. yuan.gao@csiro.au
Yuan
Y
Gao
Nicholas R F
NR
Hannan
Stephen
S
Wanyonyi
Nicky
N
Konstantopolous
Joanne
J
Pagnon
Helen C
HC
Feng
Jeremy B M
JB
Jowett
Kee-Hong
KH
Kim
Ken
K
Walder
Greg R
GR
Collier
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