Angiotensin type 1 receptor antagonist inhibits lipopolysaccharide-induced stimulation of rat microglial cells by suppressing nuclear factor κB and activator protein-1 activation

2008 ◽  
Vol 27 (2) ◽  
pp. 343-351 ◽  
Author(s):  
Michio Miyoshi ◽  
Kanako Miyano ◽  
Naoki Moriyama ◽  
Makoto Taniguchi ◽  
Tatsuo Watanabe
Keyword(s):  
Receptor Antagonist ◽  
Nuclear Factor Κb ◽  
Microglial Cells ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
Angiotensin Type ◽  
Stimulation Of

scholarly journals Differential involvement of nuclear factor-κB and activator protein-1 pathways in the interleukin-1β-mediated decrease of deiodinase type 1 and thyroid hormone receptor β1 mRNA

2006 ◽  
Vol 189 (1) ◽  
pp. 37-44 ◽  
Author(s):  
J Kwakkel ◽  
W M Wiersinga ◽  
A Boelen
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Nuclear Factor Κb ◽  
Hepatoma Cell Line ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
Nfκb Pathway

One of the hallmarks of the sick euthyroid syndrome or non-thyroidal illness is a decrease of serum triiodothyronine, caused mainly by a decrease in liver deiodinase type 1 (D1) mRNA and activity. Proinflammatory cytokines like interleukin (IL)-1β are likely involved in this disease, but are also known to inhibit thyroid hormone receptor (TR)-β1 gene expression, which is of interest as the D1 promoter contains TREs. The aim of the present study was to evaluate whether the IL-1β-induced decrease of D1 and TRβ1 mRNA is mediated by the same cytokine signalling pathways in a human hepatoma cell line (HepG2). We observed a downregulation of both D1 and TRβ1 mRNA after 4 h of incubating the cells with IL-1β. Sulfasalazine was used to inhibit the nuclear factor-κB (NFκB) pathway and SP600125, a chemical inhibitor of the c-Jun N-terminal kinase, was used as an inhibitor of the activator protein-1 (AP-1) pathway. AP-1 inhibition did not affect the decrease of D1 and TRβ1 mRNA, but the TRβ1 mRNA decrease was completely abolished after inhibiting NFκB, while D1 mRNA was unaffected. Only simultaneous inhibition of both the NFκB and AP-1 pathways abolished the D1 mRNA decrease. We concluded that IL-1β stimulation of HepG2 cells results in a marked decrease of D1 and TRβ1 mRNA. The decrease of TRβ1 mRNA is exclusively mediated by the NFκB pathway, while the decrease of D1 mRNA requires inhibition of both the AP-1 and the NFκB pathways.

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