Biochemical and Biophysical Research Communications, Vol.379, No.2, 379-383, 2009
Induction of histidine decarboxylase in macrophages inhibited by the novel NF-kappa B inhibitor (-)-DHMEQ
Histamine often Causes inflammation, and this amine is produced by histidine decarboxylase (HDC). We found that ()-DHMEQ, an NF-kappa B inhibitor, inhibited lipopolysaccharide (LPS)-induced histamine production and HDC induction in mouse macrophage cell line RAW264.7. However, as there is no kappa B site in the HDC promoter, we Studied the mechanism of inhibition. Knockdown of the transcription factor C/EBP beta reduced the HDC expression in LPS-treated cells. (-)-DHMEQ inhibited the C/EBPli transcriptional activity in a reporter assay and in an electrophoresis mobility shift assay. But it did not inhibit the in vitro binding of C/EBP beta to DNA. It also did not lower the nuclear amount of C/EBP beta on the other hand, the addition of recombinant p65, a component of NF-kappa B, enhanced the activity of C/EBP beta acting as a cofactor in vitro. Then, we found that ()-DHMEQ lowered the nuclear amount of p65, Thus, inhibition of the C/EBP beta activity by (-)-DHMEQ Would be due to a reduction in the amount Of nuclear p65, which has a coactivator activity for C/EBP beta that is essential for the HDC induction. ()-DHMEQ may be useful as an anti-inflammatory agent by lowering the histamine production in the body. (c) 2008 Elsevier Inc. All rights reserved.