Selenium regulates transcription factor NF-kappaB activation during the acute phase reaction.
BACKGROUND
We reported a reciprocal relationship between reduced serum selenium (Se) and elevated serum C-reactive protein (CRP) in various pathological conditions in comparison with the levels in 141 healthy subjects. To clarify the implications of these observations, the effect of Se on nuclear factor (NF)-kappaB, which upregulates the CRP synthesis in the liver, was examined.


METHODS
Human hepatoma cell line HuH-7 was cultured in medium with 2% fetal calf serum (FCS) for 3 days for the Se deprivation, followed by another 3 days in the same medium containing sodium selenite prior to stimulation of the cells with either monocyte-conditioned medium (MoCM) or tumor necrosis factor-alpha (TNF-alpha). NF-kappaB activation and the synthesis of CRP in hepatocytes were examined by a non-radioisotope (non-RI) gel shift assay for the nuclear extract from the cells and by a highly sensitive ELISA for the cellular extract, respectively.


RESULTS
The NF-kappaB activation induced by MoCM and TNF-alpha were inhibited by Se at the physiological levels. The maximum activation of NF-kappaB was induced by TNF-alpha or MoCM at a Se concentration (0.5 approximately 1 micromol/l) which was half the level of the serum Se in healthy subjects and was equivalent to level in subjects with pathological conditions together with high serum CRP values. Under the same conditions, the hepatocytes synthesized maximal amounts of CRP.


CONCLUSIONS
Selenium at physiological levels mediates inhibition of the activation of the transcription factor NF-kappaB which regulates genes that encode inflammatory cytokines, and that conversely, the reduction of selenium induces the synthesis of CRP by hepatocytes during the acute phase response.
Maehira
Fusako
F
Laboratory of Clinical Biochemistry, Department of Health Technology, School of Health Sciences, University of the Ryukyus, Okinawa 903-0215, Japan. fmaehira@med.u.ryukyu.ac.jp
Miyagi
Ikuko
I
Eguchi
Yukinori
Y
D000210:Acute-Phase Reaction / Q000235:genetics / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis*; D012643:Selenium / Q000494:pharmacology*; D013879:Thioredoxins / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016207:Cytokines; D016328:NF-kappa B; D013879:Thioredoxins; D002097:C-Reactive Protein; D012643:Selenium