Document Detail

Cell-Type-Specific Down-Regulation of Heme Oxygenase-1 by Lipopolysaccharide via Bach1 in Primary Human Mononuclear Cells.
MedLine Citation:
PMID:  25463280     Owner:  NLM     Status:  Publisher    
Heme oxygenase (HO)-1 is the inducible isoform of heme degradation, which is up-regulated by multiple stress stimuli. HO-1 has major immunomodulatory and anti-inflammatory effects via its cell-type-specific functions in mononuclear cells. Contradictory findings have been reported on HO-1 gene regulation by the toll-like receptor (TLR)4 ligand lipopolysaccharide (LPS) in these cells. Therefore, we re-investigated the effect of LPS on HO-1 gene expression in human and murine mononuclear cells in vitro and in vivo. Remarkably, LPS down-regulated HO-1 mRNA levels in primary human peripheral blood mononuclear cells (PBMCs), CD14+ monocytes, macrophages, dendritic cells and granulocytes, but up-regulated HO-1 mRNA levels in murine macrophages and human monocytic leukemia cell lines. Furthermore, experiments with human CD14+ monocytes revealed that activation of other TLRs including TLR1, -2, -5, -6, -8 and -9 decreased HO-1 mRNA expression. LPS-dependent down-regulation of HO-1 was specific, because expression of cyclooxygenase-2, NADP(H)-quinone-oxidoreductase-1 and peroxiredoxin-1 was increased under the same experimental conditions. Notably, LPS up-regulated expression of Bach1, a critical transcriptional repressor of HO-1. Moreover, knockdown of this nuclear factor enhanced basal and LPS-dependent HO-1 expression in mononuclear cells. Finally, down-regulation of HO-1 in response to LPS was confirmed in PBMCs from human individuals subjected to experimental endotoxemia. In summary, LPS down-regulates HO-1 expression in primary human mononuclear cells via a Bach1-mediated pathway. Since LPS-dependent HO-1 regulation is cell-type- and species-specific, experimental findings in cell lines and animal models need careful interpretation.
Mirrin J Dorresteijn; Ananta Paine; Eva Zilian; Maaike G E Fenten; Eileen Frenzel; Sabina Janciauskiene; Constanca Figueiredo; Britta Eiz-Vesper; Rainer Blasczyk; Douwe Dekker; Bas Pennings; Alwin Scharstuhl; Paul Smits; Jan Larmann; Gregor Theilmeier; Johannes G van der Hoeven; Frank A D T G Wagener; Peter Pickkers; Stephan Immenschuh
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-5
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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