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Title: Induction of histidine decarboxylase in macrophages inhibited by the novel NF-{kappa}B inhibitor (-)-DHMEQ

Abstract

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/EBP{beta} 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 co-activator 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.

Authors:
 [1]; ;  [1]
  1. Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061 (Japan)
Publication Date:
OSTI Identifier:
21255863
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 379; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2008.12.065; PII: S0006-291X(08)02467-4; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIPYRETICS; DECARBOXYLASES; ELECTROPHORESIS; HISTAMINE; HISTIDINE; IN VITRO; INFLAMMATION; INHIBITION; MACROPHAGES; MICE; PROMOTERS; TRANSCRIPTION FACTORS

Citation Formats

Suzuki, Eriko, Ninomiya, Yoko, and Umezawa, Kazuo. Induction of histidine decarboxylase in macrophages inhibited by the novel NF-{kappa}B inhibitor (-)-DHMEQ. United States: N. p., 2009. Web. doi:10.1016/j.bbrc.2008.12.065.
Suzuki, Eriko, Ninomiya, Yoko, & Umezawa, Kazuo. Induction of histidine decarboxylase in macrophages inhibited by the novel NF-{kappa}B inhibitor (-)-DHMEQ. United States. https://doi.org/10.1016/j.bbrc.2008.12.065
Suzuki, Eriko, Ninomiya, Yoko, and Umezawa, Kazuo. 2009. "Induction of histidine decarboxylase in macrophages inhibited by the novel NF-{kappa}B inhibitor (-)-DHMEQ". United States. https://doi.org/10.1016/j.bbrc.2008.12.065.
@article{osti_21255863,
title = {Induction of histidine decarboxylase in macrophages inhibited by the novel NF-{kappa}B inhibitor (-)-DHMEQ},
author = {Suzuki, Eriko and Ninomiya, Yoko and Umezawa, Kazuo},
abstractNote = {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/EBP{beta} 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 co-activator 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.},
doi = {10.1016/j.bbrc.2008.12.065},
url = {https://www.osti.gov/biblio/21255863}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 379,
place = {United States},
year = {Fri Feb 06 00:00:00 EST 2009},
month = {Fri Feb 06 00:00:00 EST 2009}
}