Open AccessMECHANISMS OF OXIDANT REGULATION OF MONOCYTE CHEMOTACTIC PROTEIN 1 PRODUCTION IN HUMAN WHOLE BLOOD AND ISOLATED MONONUCLEAR CELLS
Author(s) -
Liyu Xing,
Daniel G. Remick
Publication year - 2007
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/shk.0b013e3180311cf4
Subject(s) - peripheral blood mononuclear cell , chemistry , monocyte , whole blood , microbiology and biotechnology , cycloheximide , lipopolysaccharide , tumor necrosis factor alpha , biochemistry , biology , endocrinology , immunology , protein biosynthesis , in vitro
Previous work has demonstrated that reactive oxygen intermediates (ROIs) play an important regulatory role in the induction of monocyte chemotactic protein 1 (MCP-1) in certain cells. This study investigated the mechanisms of ROI regulation of MCP-1 gene expression in whole blood and isolated peripheral blood mononuclear cells (PBMCs). The antioxidants dimethyl sulfoxide (DMSO), N-acetyl cysteine, and dimethyl thiourea significantly inhibited lipopolysaccharide (LPS)-induced MCP-1 production in either whole blood or isolated blood cells. In contrast, interleukin 6 and tumor necrosis factor production were not affected and interleukin-1beta levels were actually increased with DMSO treatment. Exogenous ROI (either hydrogen peroxide or O2 generated by xanthine/xanthine oxidase) stimulated MCP-1 production, which was also inhibited by DMSO. To confirm the biological relevance of these findings in vivo, mice treated with DMSO before LPS challenge had significantly lower plasma levels of MCP-1. The level of inhibition was addressed in experiments which demonstrated that DMSO significantly decreased MCP-1 mRNA induced by LPS in whole blood and PBMCs. Cycloheximide treatment did not abolish the DMSO inhibition of MCP-1 mRNA, demonstrating that de novo protein synthesis is not required. Treatment with actinomycin D showed that DMSO did not increase the decay rate of MCP-1 mRNA, indicating that ROI did not change the stability of MCP-1 mRNA. These results provide evidence that in whole blood and PBMCs, DMSO regulates MCP-1 gene expression by decreasing the induction of MCP-1 mRNA.